1: J Nutr. 2004 May;134(5):1051-1057.
A Solid Dietary Fat Containing Fish Oil Redistributes Lipoprotein Subclasses
without Increasing Oxidative Stress in Men.
Tholstrup T, Hellgren LI, Petersen M, Basu S, Straarup EM, Schnohr P, Sandstrom
B.
Centre for Advanced Food Studies, Department Human Nutrition, The Royal
Veterinary and Agricultural University, DK-1958 Frederiksberg, Denmark.
Biocentrum-DTU, Biochemistry and Nutrition, Technical University of Denmark,
Lyngby, Denmark. Section of Geriatrics and Clinical Nutrition Research, Faculty
of Medicine, Uppsala University, Uppsala, Sweden. The Copenhagen City Heart
Study, Bispebjerg University Hospital, Copenhagen, Denmark.
There is a demand and need for healthy solid dietary fats. However, synthetic
fats can be tailored to contain specific physiologic properties. Our goal was to
design dietary solid test fats that would be both beneficial to the atherogenic
lipid profile and stable against lipid peroxidation. Sixteen men (age 35-75 y)
substituted 80 g of their normal dietary fat intake with test fat for two
periods of 21 d each in a double-blind, randomized, crossover study. Although
solid, both test fats were low in cholesterol-raising SFA. Test fat "F"
contained 5 g/100 g long chain (n-3) fatty acids matched by oleic acid in test
fat "O." Plasma total triacylglycerol (TAG), VLDL TAG, cholesterol in VLDL, and
intermediate density lipoproteins (IDL) were lower (P < 0.05), whereas
apolipoprotein (apo) B of the large LDL-2 (d = 1031-1042 g/L) subclass, and
cholesterol of HDL(2b) subclass, were higher after intake of F than O fat (P <
0.05). There was no difference in the effect on in vivo oxidation measured as
the ratio of plasma isoprostanes F(2) to arachidonic acid and urinary
isoprostanes, whereas the vitamin E activity/plasma total lipids ratio was
higher after intake of F than O (P = 0.008). In conclusion, a solid dietary fat
containing (n-3) PUFA decreased plasma TAG, VLDL, and IDL cholesterol, and
redistributed lipoprotein subclasses in LDL and HDL, with a higher concentration
of the larger and less atherogenic subfractions. These changes took place
without an increase in oxidative stress as measured by in vivo markers.
PMID: 15113944 [PubMed]
2: Am J Clin Nutr. 2004 May;79(5):907S-12S.
Role of calcium and dairy products in energy partitioning and weight management.
Zemel MB.
University of Tennessee, Knoxville.
Dietary calcium plays a pivotal role in the regulation of energy metabolism
because high-calcium diets attenuate adipocyte lipid accretion and weight gain
during the overconsumption of an energy-dense diet and increase lipolysis and
preserve thermogenesis during caloric restriction, which thereby markedly
accelerates weight loss. Intracellular Ca(2+) plays a key regulatory role in
adipocyte lipid metabolism and triacylglycerol storage; increased intracellular
Ca(2+) results in the stimulation of lipogenic gene expression and lipogenesis
and the suppression of lipolysis, which results in increased lipid filling and
increased adiposity. Moreover, the increased calcitriol produced in response to
low-calcium diets stimulates adipocyte Ca(2+) influx and, consequently, promotes
adiposity, whereas higher-calcium diets inhibit lipogenesis, inhibit
diet-induced obesity in mice, and promote lipolysis, lipid oxidation, and
thermogenesis. Notably, dairy sources of calcium markedly attenuate weight and
fat gain and accelerate fat loss to a greater degree than do supplemental
sources of calcium. This augmented effect of dairy products relative to
supplemental calcium is likely due to additional bioactive compounds, including
the angiotensin-converting enzyme inhibitors and the rich concentration of
branched-chain amino acids in whey, which act synergistically with calcium to
attenuate adiposity. These concepts are confirmed by epidemiologic data and
recent clinical trials, which indicate that diets that include >/=="
BORDER="0">3 daily servings of dairy products result in significant reductions
in adipose tissue mass in obese humans in the absence of caloric restriction and
markedly accelerate weight and body fat loss secondary to caloric restriction
compared with diets low in dairy products. These data indicate an important role
for dairy products in both the prevention and treatment of obesity.
PMID: 15113738 [PubMed]
3: Am J Clin Nutr. 2004 May;79(5):899S-906S.
Is a calorie a calorie?
Buchholz AC, Schoeller DA.
Department of Nutritional Sciences, University of Wisconsin-Madison.
The aim of this review was to evaluate data regarding potential thermodynamic
mechanisms for increased rates of weight loss in subjects consuming diets high
in protein and/or low in carbohydrate. Studies that compared weight loss and
energy expenditure in adults consuming diets high in protein and/or low in
carbohydrate with those in adults consuming diets low in fat were reviewed. In
addition, studies that measured the metabolizable energy of proteins, fats, and
carbohydrates were reviewed. Diets high in protein and/or low in carbohydrate
produced an approximately 2.5-kg greater weight loss after 12 wk of treatment.
Neither macronutrient-specific differences in the availability of dietary energy
nor changes in energy expenditure could explain these differences in weight
loss. Thermodynamics dictate that a calorie is a calorie regardless of the
macronutrient composition of the diet. Further research on differences in the
composition of weight loss and on the influence of satiety on compliance with
energy-restricted diets is needed to explain the observed increase in weight
loss with diets high in protein and/or low in carbohydrate.
PMID: 15113737 [PubMed]
4: Am J Physiol Endocrinol Metab. 2004 Apr 27 [Epub ahead of print]
Longitudinal changes in energy expenditure and body composition in obese women
with normal and impaired glucose tolerance.
Okereke NC, Huston-Presley L, Amini SB, Kalhan S, Catalano PM.
Department of Reproductive Biology, Case Western Reserve University at
MetroHealth Medical Center, Cleveland, OH, USA.
Our primary objective was to evaluate the changes in energy expenditure and body
composition in women with normal glucose tolerance (NGT) and gestational
diabetes (GDM). A secondary objective was to examine the relationship between
maternal leptin and nutrient metabolism. Fifteen obese women 8 with NGT and 7
with GDM were evaluated prior to conception (P) at 12-14 weeks (E) and 34-36
weeks (L). Energy expenditure and glucose and fat metabolism were measured using
indirect calorimetry. Basal hepatic glucose production was measured using [6,6
(2)H2] glucose and insulin sensitivity by the euglycemic clamp. There was a
significant increase (6.6 kg, p=0.0001) in fat mass (FM) from time P to L. There
was a 30% (p=0.0001) increase in basal VO2 (ml/min). There were no significant
changes in carbohydrate oxidation during fasting or storage from P to L. There
was, however, a significant (p=0.0001) 150% increase in basal fat oxidation
(mg/min) from P to L. Under hyperinsulinemic conditions there were similar 25%
increases in VO2 (p=0.0001) from P to L in both groups. Because of the
significant increases in insulin resistance from P to L, there was a significant
(p=0.0001) decrease in carbohydrate oxidation and storage. There was a net
change from lipogenesis to lipolysis, i.e. fat oxidation (30- 40 mg/min,
p=0.0001) from P to L. Serum leptin concentrations had a significant positive
correlation with fat oxidation at time E (r=0.76, p=0.005) and L (r=0.72,
p=0.009). Pregnancy in obese women is associated with significant increases in
fat mass, basal metabolic rate and an increased reliance on lipids both in the
basal state and during the clamp. These modifications are similar in women with
NGT and GDM. The increased reliance on fat metabolism is accompanied by a
concomitant decrease in carbohydrate metabolism during hyperinsulinemia. The
increase in fat oxidation may be related to increased maternal serum leptin.
PMID: 15113705 [PubMed]
5: Int J Obes Relat Metab Disord. 2004 Apr 27 [Epub ahead of print]
Resistance to the orexigenic effect of ghrelin in dietary-induced obesity in
mice: reversal upon weight loss.
Perreault M, Istrate N, Wang L, Nichols AJ, Tozzo E, Stricker-Krongrad A.
1Metabolic Diseases Biology Department, Millennium Pharmaceuticals Inc.,
Cambridge, MA, USA.
BACKGROUND:: Ghrelin, an endogenous ligand for growth hormone secretagogue
receptor (GHS-R), is known to increase food intake in lean humans and rodents.
In addition, ghrelin levels are increased by fasting in lean rodents and are
elevated before meals in humans, suggesting an important role for ghrelin in
meal initiation. However, in obese human, circulating ghrelin levels were found
to be significantly reduced as compared to lean individuals. OBJECTIVES:: To
evaluate whether circulating ghrelin levels, as well as ghrelin sensitivity, are
decreased in obese individuals in order to limit its effect on food intake.
DESIGN:: Lean C57BL/6J mice fed a chow, a low- (LFD) or a high-fat diet (HFD)
were used to determine ghrelin regulation and secretion as well as ghrelin
sensitivity. MEASUREMENTS:: Plasma ghrelin levels were measured in low- and
high-fat fed mice. Ghrelin-induced food intake was measured in chow, low- and
high-fat fed mice. RESULTS:: We measured ghrelin levels in lean and diet-induced
obese mice, fed on an LFD or an HFD, respectively. We observed that not only
ghrelin secretion was reduced in obese mice but its diurnal regulation was also
lost. In addition, we failed to observe any change in ghrelin secretion upon
fasting and refeeding. Moreover, we observed that the sensitivity to the
orexigenic effects of exogenous ghrelin was reduced in obese mice when compared
to lean mice fed a chow or a LFD. The insensitivity of obese mice to ghrelin was
improved upon weigh loss. CONCLUSION:: Altogether, these results indicate that
ghrelin secretion and regulation is impaired in dietary-induced obesity in mice
and suggest that ghrelin inhibition could prevent weight regain after weight
loss.International Journal of Obesity advance online publication, 27 April 2004;
doi:10.1038/sj.ijo.0802640
PMID: 15111983 [PubMed]
6: Diabetes Care. 2004 May;27(5):1077-80.
Orlistat augments postprandial increases in glucagon-like peptide 1 in obese
type 2 diabetic patients.
Damci T, Yalin S, Balci H, Osar Z, Korugan U, Ozyazar M, Ilkova H.
Istanbul University Cerrahpasa Medical School, Department of Internal Medicine,
Division of Endocrinology Diabetes and Metabolism, Istanbul, Turkey.
tdamci@superonline.com
OBJECTIVE: Orlistat leads to improved glycemic control in obese type 2 diabetic
patients, which is attributed to decreased insulin resistance associated with
weight loss. Glucagon-like peptide 1 (GLP-1) and glucose-dependent
insulinotropic peptide (GIP) are gut hormones that are secreted in response to
food intake, and they both stimulate insulin secretion. Orlistat decreases fat
absorption and increases intestinal fat content, which may lead to increased
secretion of these peptides. In this pilot study, we tested the hypothesis that
increased levels of these intestinal hormones may be involved in the improvement
of postprandial hyperglycemia observed previously with orlistat in type 2
diabetic patients. RESEARCH DESIGN AND METHODS: A total of 29 type 2 diabetic
patients, who were not taking insulin or alpha-glucosidase inhibitors, were
enrolled in the study. On a crossover and single-blind design, after an
overnight fasting, the patients received 120-mg orlistat or placebo capsules,
followed by a standard 600-kcal mixed meal that contained 38% fat. At baseline
and 60 min after the meal, blood samples were obtained for the measurement of
GLP-1, GIP, insulin, C-peptide, triglycerides, free fatty acids, and glucose.
RESULTS: All measured parameters increased significantly in response to the
mixed meal compared with baseline, both with orlistat or placebo. When compared
with the placebo, the orlistat administration resulted in a significantly
enhanced postprandial increase in GLP-1 and C-peptide levels and attenuated the
postprandial rise in glucose and triglycerides. CONCLUSIONS: The results of this
study suggest that apart from decreasing insulin resistance as a result of
weight loss, orlistat may increase postprandial GLP-1 levels, thereby enhancing
the insulin secretory response to the meal and blunting the postprandial rise in
glucose in type 2 diabetic patients. Increased GLP-1 levels, which lead to
decreased food intake, may also contribute to the weight loss that is associated
with the use of this drug.
PMID: 15111524 [PubMed]
7: Sports Med. 2004;34(5):317-327.
Macronutrient Considerations for the Sport of Bodybuilding.
Lambert CP, Frank LL, Evans WJ.
Nutrition, Metabolism, and Exercise Laboratory, Donald W. Reynolds Center on
Aging, Department of Geriatrics, University of Arkansas for Medical Sciences and
Geriatric Research, Education and Clinical Center, Central Arkansas Veterans
Healthcare System, Little Rock, Arkansas, USA.
Participants in the sport of bodybuilding are judged by appearance rather than
performance. In this respect, increased muscle size and definition are critical
elements of success. The purpose of this review is to evaluate the literature
and provide recommendations regarding macronutrient intake during both
'off-season' and 'pre-contest' phases. Body builders attempt to increase muscle
mass during the off-season (no competitive events), which may be the great
majority of the year. During the off-season, it is advantageous for the
bodybuilder to be in positive energy balance so that extra energy is available
for muscle anabolism. Additionally, during the off-season, adequate protein must
be available to provide amino acids for protein synthesis. For 6-12 weeks prior
to competition, body builders attempt to retain muscle mass and reduce body fat
to very low levels. During the pre-contest phase, the bodybuilder should be in
negative energy balance so that body fat can be oxidised. Furthermore, during
the pre-contest phase, protein intake must be adequate to maintain muscle mass.
There is evidence that a relatively high protein intake (~30% of energy intake)
will reduce lean mass loss relative to a lower protein intake (~15% of energy
intake) during energy restriction. The higher protein intake will also provide a
relatively large thermic effect that may aid in reducing body fat. In both the
off-season and pre-contest phases, adequate dietary carbohydrate should be
ingested (55-60% of total energy intake) so that training intensity can be
maintained. Excess dietary saturated fat can exacerbate coronary artery disease;
however, low-fat diets result in a reduction in circulating testosterone. Thus,
we suggest dietary fats comprise 15-20% of the body builders' off-season and
pre-contest diets.Consumption of protein/amino acids and carbohydrate
immediately before and after training sessions may augment protein synthesis,
muscle glycogen resynthesis and reduce protein degradation. The optimal rate of
carbohydrate ingested immediately after a training session should be 1.2
g/kg/hour at 30-minute intervals for 4 hours and the carbohydrate should be of
high glycaemic index. In summary, the composition of diets for body builders
should be 55-60% carbohydrate, 25-30% protein and 15-20% of fat, for both the
off-season and pre-contest phases. During the off-season the diet should be
slightly hyperenergetic (~15% increase in energy intake) and during the
pre-contest phase the diet should be hypoenergetic (~15% decrease in energy
intake).
PMID: 15107010 [PubMed]
8: Ter Arkh. 2004;76(2):40-4.
[In Process Citation]
[Article in Russian]
[No authors listed]
AIM: To study morphological alterations in small intestinal wall in patients
with chronic cardiac failure (CCF) of various severity and their relations with
functional condition of the small intestine. MATERIAL AND METHODS: 63 patients
(mean age 58.7 years) entered an open cohort study. By CCF and body mass index
(BMI) the patients were divided into 4 groups. Estimation of ejection fraction
(EF), BMI and lean body mass (LBM) was made in all the patients as well as
functional intestinal activity was assessed by fat excretion and fecal protein.
Small intestinal biopsies were made endoscopically for collagen quantitation.
RESULTS: A rise in collagen content in the small intestine correlated with
severity of CCF. In patients free of CCF relative area of collagen averaged
12.8%, in CCF FC I-II--16.5%, in CCF FC III-IV with cachexia--32.4%. Greater
fibrosis of the small intestine corresponded to greater malabsorption. A 3-fold
increase in collagen area led to a 2-3-fold growth in protein and fat loss with
feces. In CCF, LBM was subnormal while body mass reduction correlated with
relative collagen area. CONCLUSION: Morphofunctional changes of the small
intestine developing in parallel with CCF severity lead to a significant loss in
basic nutrients, regression of LBM and development of protein-energy
insufficiency in patients with CCF.
PMID: 15106413 [PubMed]
9: J Clin Endocrinol Metab. 2004 Apr;89(4):1753-9.
Further lowering of muscle lipid oxidative capacity in obese subjects after
biliopancreatic diversion.
Fabris R, Mingrone G, Milan G, Manco M, Granzotto M, Dalla Pozza A, Scarda A,
Serra R, Greco AV, Federspil G, Vettor R.
Endocrine-Metabolic Laboratory, Internal Medicine, Department of Medical and
Surgical Sciences, University of Padova, 35128 Padova, Italy.
A reduced lipid oxidative capacity is considered a risk factor for the
development of obesity, but a further impairment of lipid oxidative capacity is
observed after weight loss. We aimed to define the mechanisms underlying this
phenomenon in skeletal muscle and in particular to study the mitochondrial and
peroxisomal lipid oxidative pathways. Thus we measured intramyocellular
triglyceride content (IMTG) and the expression of genes of lipid oxidation
[peroxisome proliferator-activated receptor-alpha, carnitine
palmitoyltransferase 1B, and acyl-coenzyme A (acyl-CoA) oxidase 1] and synthesis
(acetyl-CoA carboxylase B) using RT-PCR analysis in muscle biopsies of morbidly
obese patients before and after biliopancreatic diversion. Weight reduction
significantly decreased IMTG while increasing insulin sensitivity, measured by
euglycemic hyperinsulinemic clamp. Moreover, an increase in glucose and a
decline in lipid oxidation, as assessed by respiratory chamber, were observed.
Weight loss reduced the expression of peroxisome proliferator-activated
receptor-alpha (-46.7%), carnitine palmitoyltransferase 1B (-43.1%), acyl-CoA
oxidase 1 (-37.8%), and acetyl-CoA carboxylase B (-48.7%). Our results indicate
that a defect of both peroxisomal and mitochondrial oxidative pathways at the
muscular level may contribute to the reduced fat oxidation in obese subjects
after biliopancreatic diversion. They also suggest that a depression of the de
novo lipogenesis may account for IMTG depletion.
PMID: 15070941 [PubMed]
10: J Bone Miner Res. 2004 May;19(5):830-40.
Oxysterols regulate differentiation of mesenchymal stem cells: pro-bone and
anti-fat.
Kha HT, Basseri B, Shouhed D, Richardson J, Tetradis S, Hahn TJ, Parhami F.
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles,
California, USA.
Pluripotent mesenchymal stem cells can undergo lineage-specific differentiation
in adult organisms. However, understanding of the factors and mechanisms that
drive this differentiation is limited. We show the novel ability of specific
oxysterols to regulate lineage-specific differentiation of mesenchymal stem
cells into osteogenic cells while inhibiting their adipogenic differentiation.
Such effects may have important implications for intervention with osteoporosis.
INTRODUCTION: Oxysterols are products of cholesterol oxidation and are formed in
vivo by a variety of cells including osteoblasts. Novel pro-osteogenic and
anti-adipogenic effects of specific oxysterols on pluripotent mesenchymal cells
are demonstrated in this report. Aging and osteoporosis are associated with a
decrease in the number and activity of osteoblastic cells and a parallel
increase in the number of adipocytic cells. MATERIALS AND METHODS: The M2-10B4
pluripotent marrow stromal cell line, as well as several other mesenchymal cell
lines and primary marrow stromal cells, was used to assess the effects of
oxysterols. All results were analyzed for statistical significance using ANOVA.
RESULTS AND CONCLUSION: Pro-osteogenic and anti-adipogenic effects of specific
oxysterols were assessed by the increase in early and late markers of osteogenic
differentiation, including alkaline phosphatase activity, osteocalcin mRNA
expression and mineralization, and the decrease in markers of adipogenic
differentiation including lipoprotein lipase and adipocyte P2 mRNA expression
and adipocyte formation. Complete osteogenic differentiation of M2 cells into
cells expressing early and late markers of differentiation was achieved only
when using combinations of specific oxysterols, whereas inhibition of
adipogenesis could be achieved with individual oxysterols. Oxysterol effects
were in part mediated by extracellular signal-regulated kinase and enzymes in
the arachidonic acid metabolic pathway, i.e., cyclo-oxygenase and phospholipase
A(2). Furthermore, we show that these specific oxysterols act in synergy with
bone morphogenetic protein 2 in inducing osteogenic differentiation. These
findings suggest that oxysterols may play an important role in the
differentiation of mesenchymal stem cells and may have significant, previously
unrecognized, importance in stem cell biology and potential therapeutic
interventions.
PMID: 15068507 [PubMed]
11: Mech Ageing Dev. 2004 Apr;125(4):297-304.
Effects of testosterone on body composition of the aging male.
Mudali S, Dobs AS.
Johns Hopkins University School of Medicine, Baltimore, MD 21208, USA.
The aging process is accompanied by significant changes in body composition
characterized by decreased fat free mass and increased and redistributed fat
mass. Muscle loss results from the atrophy of muscle fibers and decreased
synthesis of muscle proteins. Increased number of adipocytes and fat
accumulation in non-adipose tissue leads to adiposity. These changes can impose
functional limitations and increase morbidity. In men, declining testosterone
levels that occur with aging can be a contributing factor to these changes.
Studies in hypogonadal men have shown that testosterone replacement is effective
in increasing muscle mass and strength and decreasing fat mass. The molecular
mechanisms of testosterone's influence on muscle and adipose are not fully
elucidated. However, testosterone appears to stimulate IGF-1 expression directly
and indirectly leading to increased muscle protein synthesis and growth. It may
also counter the inhibitory effects of myostatin, cytokines, and
glucocorticoids. The predominant effects of testosterone on fat mass are
increased lipolysis and decreased adipogenesis. Current evidence suggests that
testosterone replacement may be effective in reversing age-dependent body
composition changes and associated morbidity. However, hypogonadism must be
diagnosed carefully, and therapy should be monitored regularly in order to avoid
the adverse effects associated with testosterone supplementation.
PMID: 15063106 [PubMed]
12: J Med Assoc Thai. 2004 Feb;87(2):166-72.
Improvement of fat redistribution, insulin resistance and hepatic fatty
infiltration in HIV-associated lipodystrophy syndrome by pioglitazone: a case
report.
Prasithsirikul W, Bunnag P.
Bamrasnaradura Institute, Nonthaburi 11000, Thailand.
HIV-associated lipodystrophy syndrome is a syndrome occurring in HIV-infected
patients who were treated with highly-active antiretroviral therapy (HAART),
especially regimen containing protease inhibitors. The syndrome consists of fat
redistribution, with loss of subcutaneous fat and increase in visceral fat, and
metabolic disturbances, including glucose intolerance or overt diabetes and
dyslipidemia. No standard treatment has been established for this syndrome.
Pioglitazone is an oral antidiabetic agent that acts primarily on adipose tissue
to reduce insulin resistance. The authors report a 50-year old HIV-infected
woman who developed HIV-associated lipodystrophy syndrome after 3 months of
HAART. She had significant weight loss with obvious loss of subcutaneous fat,
together with development of hypertension, diabetes and dyslipidemia. After
treatment with 30 milligrams of pioglitazone daily, her body weight increased
within the first month of treatment. Subcutaneous fat loss was restored.
Improvement in glycemic and lipid control was also noted. CT scan of the abdomen
revealed that fatty infiltration in the liver was markedly decreased. Visceral
fat as assessed by CT scan had also decreased. Pioglitazone appeared to have
beneficial effects in this patient.
Publication Types:
Case Reports
PMID: 15061300 [PubMed]
13: Endocrinology. 2004 Apr 1 [Epub ahead of print]
Estrogen and raloxifene modulate leptin and its receptor in hypothalamus and
adipose tissue from ovariectomized rats.
Meli R, Pacilio M, Mattace Raso G, Esposito E, Coppola A, Nasti A, Di Carlo C,
Nappi C, Di Carlo R.
Department of Experimental Pharmacology, *Department of Obstetrics and
Gynaecology, University of Naples Federico II, Naples, Italy.
Obesity, from declining estrogen levels after menopause, increases the risk of
heart disease, diabetes, and hypertension. Ovariectomy in rats is a good model
of estrogen insufficiency. The ensuing mild obesity is useful to study how
hypoestrogenism alters adiposity. This study aims to examine the hypothesis that
in ovariectomized rats modification in estrogen levels or a treatment with a
selective estrogen receptor modulator raloxifene (RAL) alters leptinemia and
modulates leptin receptor (Ob-R) abundance in hypothalamus and white adipose
tissue, in replay to modification of adipose status induced by hypoestrogenism.
Mid- and long-term studies (7 and 22 weeks) were conducted to monitor the change
of leptinemia in rats after estrogen loss by ovariectomy (OVX), estrogen
replacement by 17-beta-estradiol (OVX+E2) or RAL treatment (OVX+RAL). Leptin was
significantly higher in OVX rats vs. controls, in a time dependent manner. This
effect was reversed both by E2 or RAL treatment at 7 (P < 0.05) and 22 weeks (P
< 0.001). Moreover, E2- or RAL-treatment reverted ovariectomy-induced increase
of food intake, body weight and fat mass content; the modifications of serum
parameters were examined to evaluate the different lipid profile. We also
evaluated Ob-R expression in hypothalamus and adipose tissue by Western blot
analysis. The expression of the long functional isoform (Ob-Rb) increased at 7
weeks only in adipose tissue and decreased at 22 weeks in OVX rats in both
tissues and these effects were reversed by E2 or RAL treatment. We provide
evidence that central and peripheral Ob-Rb expression is related to modification
of estrogen levels.
PMID: 15059958 [PubMed]
14: Eur J Nutr. 2004 Mar;43 Suppl 1:I6-I11.
What are the health effects of fat?
Wahrburg U.
Fachhochschule Munster, Fachbereich Oecotrophologie, Corrensstr. 25, 48149,
Munster, Germany, uwahrburg@fh-muenster.de
In order to answer the question which health benefits are to be expected from
dietary fat, we have to differentiate between different kinds of fat with
varying fatty acid composition. Saturated fatty acids are commonly judged to
have a negative health impact as they lead to increased serum cholesterol levels
and a higher risk of coronary heart disease. Therefore, all recommendations
stress the importance to limit the intake of saturated fatty acids.
Monounsaturated fatty acids, on the other hand, have a positive impact on the
serum lipid profile, lead to decreased LDL-oxidation and favorably influence the
metabolism of diabetics. However, it is essential that monounsaturated fatty
acids be mainly supplied by plant oils like rape seed or olive oil and not by
foods that are simultaneously rich in saturated fatty acids. Concerning
polyunsaturated fatty acids, it is important to increase the supply of n-3 fatty
acids (ratio of n-6:n-3: about 5:1) as there is substantial evidence for their
protective effects. If the fatty acid composition of the diet is optimized, even
a total dietary fat content of 35% of total energy intake can be adequate as
long as there is enough physical activity and the diet is rich in plant-derived
foods like vegetables, fruits, cereals, potatoes, beans and legumes.
PMID: 15052493 [PubMed]
15: J Nutr. 2004 Apr;134(4):968S-73S.
Dietary protein impact on glycemic control during weight loss.
Layman DK, Baum JI.
Department of Food Science and Human Nutrition, University of Illinois
Urbana-Champaign, Urbana, IL 61801, USA. dlayman@uiuc.edu
Diets with higher protein (1.5 g x kg(-1) x d(-1)) and reduced carbohydrates
(120 to 200 g/d) appear to enhance weight loss due to a higher loss of body fat
and reduced loss of lean body mass. While studies of prolonged use of moderate
protein diets are not available, short-term studies report beneficial effects
associated with increased satiety, increased thermogenesis, sparing of muscle
protein loss, and enhanced glycemic control. Combined impacts of a moderate
protein diet are likely derived from lower carbohydrates resulting in lower
postprandial increase in blood glucose and lower insulin response, and higher
protein providing increased BCAA leucine levels and gluconeogenic substrates. A
key element in the diet appears to be the higher intake of BCAA leucine with
unique regulatory actions on muscle protein synthesis, modulation of the insulin
signal, and sparing of glucose use by stimulation of the glucose-alanine cycle.
This review focuses on the contributions of leucine and the BCAA to regulation
of muscle protein synthesis and glycemic control.
Publication Types:
Review
Review, Tutorial
PMID: 15051856 [PubMed]
16: J Nutr. 2004 Apr;134(4):880-5.
Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial
lipemia differently in overweight men.
Sharman MJ, Gomez AL, Kraemer WJ, Volek JS.
Department of Kinesiology, University of Connecticut, Storrs, CT 06269-1110,
USA. matthew.sharman@uconn.edu
Hypoenergetic very low-carbohydrate and low-fat diets are both commonly used for
short-term weight loss; however, few studies have directly compared their effect
on blood lipids, with no studies to our knowledge comparing postprandial
lipemia, an important independently identified cardiovascular risk factor. The
primary purpose of this study was to compare the effects of a very
low-carbohydrate and a low-fat diet on fasting blood lipids and postprandial
lipemia in overweight men. In a balanced, randomized, crossover design,
overweight men (n = 15; body fat >25%; BMI, 34 kg/m(2)) consumed 2 experimental
diets for 2 consecutive 6-wk periods. One was a very low-carbohydrate (<10%
energy as carbohydrate) diet and the other a low-fat (<30% energy as fat) diet.
Blood was drawn from fasting subjects on separate days and an oral fat tolerance
test was performed at baseline, after the very low-carbohydrate diet period, and
after the low-fat diet period. Both diets had the same effect on serum total
cholesterol, serum insulin, and homeostasis model analysis-insulin resistance
(HOMA-IR). Neither diet affected serum HDL cholesterol (HDL-C) or oxidized LDL
(oxLDL) concentrations. Serum LDL cholesterol (LDL-C) was reduced (P < 0.05)
only by the low-fat diet (-18%). Fasting serum triacylglycerol (TAG), the
TAG/HDL-C ratio, and glucose were significantly reduced only by the very
low-carbohydrate diet (-44, -42, and -6%, respectively). Postprandial lipemia
was significantly reduced when the men consumed both diets compared with
baseline, but the reduction was significantly greater after intake of the very
low-carbohydrate diet. Mean and peak LDL particle size increased only after the
very low-carbohydrate diet. The short-term hypoenergetic low-fat diet was more
effective at lowering serum LDL-C, but the very low-carbohydrate diet was more
effective at improving characteristics of the metabolic syndrome as shown by a
decrease in fasting serum TAG, the TAG/HDL-C ratio, postprandial lipemia, serum
glucose, an increase in LDL particle size, and also greater weight loss (P <
0.05).
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15051841 [PubMed]
17: J Am Coll Nutr. 2004 Apr;23(2):102-7.
Long-term nutritional and digestive consequences of pelvic radiation.
Pia de la Maza M, Agudelo GM, Yudin T, Gattas V, Barrera G, Bunout D, Hirsch S.
Institute of Nutrition and Food Technology (INTA)-University of Chile, Santiago,
Chile. mpmaza@uec.inta.uchile.cl
OBJECTIVE: To study long-term changes in nutritional status and gastrointestinal
(GI) functions of 15 women previously treated with radiotherapy for
gynecological cancer. Two years prior to this research, these patients had been
assessed twice: before external radiotherapy and 5 weeks later, at the
completion of the external dose (45-50 Gy). METHODS: Each patient was given
complete clinical evaluation, consisting of dietary, physical activity and
digestive symptoms questionnaires. Blood was drawn for routine clinical
laboratory tests (hemoglobin, white blood cell count, creatinine, lipoproteins,
glucose, total proteins, albumin, and C reactive protein). Body composition was
assessed by classical anthropometric indicators and double beam X-ray
absorptiometry (DEXA), while muscle strength was measured through a hand
dynamometer. Resting energy expenditure (REE), obtained by indirect calorimetry,
was subtracted from energy ingestion, derived from dietary records, to calculate
energy balance. RESULTS: This third evaluation included fifteen patients. A
significant increase in body mass index (BMI), % body fat and waist
circumference were observed in comparison to earlier evaluations. The lean
compartment decreased significantly, and REE descended in parallel. Meanwhile,
total energy, fat and protein intake increased, compared to previous
measurements. The changes in bowel habits observed during radiotherapy persisted
at this third evaluation, with the exception of diarrhea, which was less
reported. Abdominal bloating and rectal symptoms were the most prevalent
complaints. CONCLUSIONS: After radiation treatment for gynecological cancer,
patients gained more body fat than expected in Chilean women around menopause.
In spite of high protein ingestion, the loss of fat-free mass observed during
radiation treatment was not recovered along with weight increase. This is
probably associated with infrequent physical activity, both during and after
treatment, and hyperphagia.
PMID: 15047675 [PubMed]
18: Diabetes. 2004 Apr;53(4):1007-19.
A role for the malonyl-CoA/long-chain acyl-CoA pathway of lipid signaling in the
regulation of insulin secretion in response to both fuel and nonfuel stimuli.
Roduit R, Nolan C, Alarcon C, Moore P, Barbeau A, Delghingaro-Augusto V,
Przybykowski E, Morin J, Masse F, Massie B, Ruderman N, Rhodes C, Poitout V,
Prentki M.
Molecular Nutrition Unit, Department of Nutrition, University of Montreal and
the Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.
The malonyl-CoA/long-chain acyl-CoA (LC-CoA) model of glucose-induced insulin
secretion (GIIS) predicts that malonyl-CoA derived from glucose metabolism
inhibits fatty acid oxidation, thereby increasing the availability of LC-CoA for
lipid signaling to cellular processes involved in exocytosis. For directly
testing the model, INSr3 cell clones overexpressing malonyl-CoA decarboxylase in
the cytosol (MCDc) in a tetracycline regulatable manner were generated, and
INS(832/13) and rat islets were infected with MCDc-expressing adenoviruses. MCD
activity was increased more than fivefold, and the malonyl-CoA content was
markedly diminished. This was associated with enhanced fat oxidation at high
glucose, a suppression of the glucose-induced increase in cellular free fatty
acid (FFA) content, and reduced partitioning at elevated glucose of exogenous
palmitate into lipid esterification products. MCDc overexpression, in the
presence of exogenous FFAs but not in their absence, reduced GIIS in all
beta-cell lines and in rat islets. It also markedly curtailed the stimulation of
insulin secretion by other fuel and nonfuel secretagogues. In the absence of
MCDc overexpression, the secretory responses to all types of secretagogues were
amplified by the provision of exogenous fatty acids. In the presence of
exogenous FFAs, the fatty acyl-CoA synthetase inhibitor triacsin C reduced
secretion in response to glucose and nonfuel stimuli. The data show the
existence of important links between the metabolic coupling factor malonyl-CoA,
the partitioning of fatty acids, and the stimulation of insulin secretion to
both fuel and nonfuel stimuli.
PMID: 15047616 [PubMed]
19: Physiol Res. 2004;53(2):229-34.
Quantification of intra-abdominal fat during controlled weight reduction:
assessment using the water-suppressed breath-hold MRI technique.
Tintera J, Harantova P, Suchanek P, Dvorakova A, Adamova M, Hajek M, Poledne R.
Institute of Clinical and Experimental Medicine, Videnska 1958/59, 140 00 Prague
4, Czech Republic. jati@medicon.cz
A group of 14 healthy female subjects was studied using MRI during 2 months of
life-style intervention. A series of 21 water-suppressed images was used to
determine the intra-abdominal fat volume before and after the controlled loss of
weight. The average weight decrease was 8.2 %, but the average relative loss of
visceral fat was 20.3 %, whereas subcutaneous fat decreased by 13.4 %. A small
but significant increase of insulin sensitivity (decrease in fasting insulin and
blood glucose) was observed, but no changes in lipoprotein parameters were
demonstrated. There was a significant negative correlation (r=-0.633, p=0.028)
between the relative abdominal fat decrease and the initial amount of
subcutaneous fat.
PMID: 15046562 [PubMed]
20: Metabolism. 2004 Apr;53(4):430-4.
Modest weight loss and reduction in waist circumference after medical treatment
are associated with favorable changes in serum adipocytokines.
Valsamakis G, McTernan PG, Chetty R, Al Daghri N, Field A, Hanif W, Barnett AH,
Kumar S.
Department of Diabetes and Endocrinology, Birmingham Heartlands Hospital,
Birmingham, UK.
Modest weight loss if maintained is associated with significant metabolic
benefits and reduction in cardiovascular risk. Adipose tissue secretes cytokines
believed to contribute to the pathogenesis of insulin resistance and
cardiovascular risk. We therefore observed the effect of modest weight loss on
serum adipocytokines and their relationship with changes in anthropometric and
metabolic parameters within a period of 6 months in the setting of a routine
obesity hospital clinic after various medical treatments. In this prospective,
nonrandomized, nonblinded observational study, patients were first given
treatment (sibutramine or orlistat) as decided by the treating clinician and
then allocated into 1 of 2 groups according to the treatment prescribed. The
first group included 21 Caucasian nondiabetic female subjects, with a mean
(+/-SD) age of 43 +/- 11 years and a mean body mass index (BMI) of 46 +/- 8.6
kg/m(2); subjects were treated with sibutramine 10 or 15 mg/d for weight loss.
The second group included 20 Caucasian nondiabetic female subjects, mean age 42
+/- 9 years and mean BMI 45.2 +/- 5.2 kg/m(2); orlistat was introduced after 1
month on a low-fat (5%) after
medical treatment in a routine obesity hospital clinic is associated with
improvements in insulin sensitivity and lipid profile. Modest weight loss is
also associated with potentially favourably changes in serum adipocytokines,
particularly in a rise of serum adiponectin. Reduction of waist circumference is
associated with a change in serum resistin.
PMID: 15045687 [PubMed]
21: Eur J Appl Physiol. 2004 Mar 26 [Epub ahead of print]
Hypohydration effects on thermoregulation during moderate exercise in the cold.
Kenefick RW, Mahood NV, Hazzard MP, Quinn TJ, Castellani JW.
Department of Kinesiology, The University of New Hampshire, New Hampshire Hall,
NH 03824, Durham, USA.
Hyperosmotic hypovolemia impairs vasoconstriction during sedentary cold
exposure. The purpose of this study was to determine whether hypohydration
alters thermoregulation and cardiovascular responses to exercise in cold air. On
four occasions, eight males [35.1 (2.7) years, 175.5 (3.1) cm, 73.3 (2.6) kg,
57.2 (2.6) ml kg(-1) min(-1) maximal oxygen uptake ( Vdot;O(2max)), 19.6 (2.4)%
fat] walked, in t-shirt, shorts, and shoes, at 50% Vdot;O(2max), for 60 min in
either a 4 degrees C (Cold) or a 25 degrees C (Temperate) environment in both
hypohydrated state (HYPO, -4% body mass) and euhydrated state (EU). During
exercise-cold stress, rectal temperature ( T(re)), mean weighted skin
temperature, heart rate (HR), cardiac output (CO), and stroke volume (SV) were
measured every 20 min. Mean weighted skin temperature values were not different
between HYPO and EU but were lower ( P<0.05) in Cold versus Temperate trials.
T(re) was not different ( P>0.05) between HYPO-Cold and EU-Cold. CO and SV were
not different within hydration states and were not different between Cold and
Temperate trials ( P<0.05). HR was not different between HYPO-Cold and EU-Cold.
These data demonstrate that moderate intensity exercise in the cold while
hypohydrated does not alter metabolic heat production, skin temperatures and
heat loss, nor does it increase thermoregulatory and cardiovascular strain.
PMID: 15045503 [PubMed]
22: Endocrinology. 2004 Mar 24 [Epub ahead of print]
CPT-1 Activity Stimulation by Cerulenin via SNS Activation Overrides Cerulenin's
Peripheral Effect.
Jin YJ, Li SZ, Zhao ZS, An JJ, Kim RY, Kim YM, Baik JH, Lim SK.
Division of Endocrinology, Department of Internal Medicine, College of Medicine,
Yonsei University, Seoul, Korea.; School of Life Sciences and Biotechnology,
Korea University, Seoul, Korea.; Brain Korea 21 Project for Medical Sciences,
Yonsei University, Seoul, Korea.; Division of Endocrinology, Department of
Internal Medicine, Affiliated Hospital, Medical College, YanBian University,
YanJi, People's Republic of China.
To clarify the paradoxic effects of cerulenin, namely, its in vitro inhibitory
effects on fat catabolism, and its in vivo reduction of fat mass, we studied the
in vivo and in vitro effects of cerulenin on carnitine palmitoyltransferase-1
(CPT-1) activity, the rate-limiting enzyme of fatty acid oxidation. A single
intraperitoneal (IP) injection of cerulenin significantly reduced body weight
and increased core temperature without significantly reducing food intake. In
situ hybridization study revealed that a single injection of cerulenin did not
affect the expression of orexigenic neuropeptide mRNA. Cerulenin's effect on
CPT-1 activity was biphasic in the liver and muscle: early suppression during
the first 1 h and late stimulation in the 3 approximately 5 h following IP
treatment. In vitro cerulenin treatment reduced CPT-1 activity, which was
overcome by co-treating with catecholamine. Intracerebroventricular injection of
cerulenin increased CPT-1 activity significantly in soleus muscle and this
effect was sustained for up to 3 h. Pretreatment with alpha-methyl-p-tyrosine
inhibited the cerulenin-induced increase in core temperature and the late phase
stimulating effect of cerulenin on CPT-1 activity. In adrenalectomized mice,
cerulenin also increased the activity. In vivo cerulenin treatment enhanced
muscle CPT-1 activity in monosodium glutamate-treated arcuate nucleus lesioned
mice, but not in gold thioglucose-treated ventromedial hypothalamus lesioned
mice. These findings suggest that cerulenin-induced late phase stimulating
effects on CPT-1 activity and energy expenditure is mediated by the activation
of innervated sympathetic nervous system neurons through the firing of undefined
neurons of the ventromedial hypothalamus, rather than the arcuate nucleus.
PMID: 15044358 [PubMed]
23: Scand J Med Sci Sports. 2004 Apr;14(2):74-99.
Fat metabolism in exercise--with special reference to training and growth
hormone administration.
Lange KH.
Sports Medicine Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
klange@dadlnet.dk
Despite abundance of fat, exclusive dependency on fat oxidation can only sustain
a metabolic rate corresponding to 50-60% of VO(2max) in humans. This puzzling
finding has been subject to intense research for many years. Lately, it has
gained renewed interest as a consequence of increased obesity and physical
inactivity imposed by Western lifestyle. Why are humans so poor at metabolizing
fat? Can fat metabolism be manipulated by exercise, training, diet and hormones?
And why is fat stored in specialized adipose tissue and not just as lipid
droplets inside muscle cells? In the present review, human fat metabolism is
discussed in relation to how human fat metabolism is designed. Limitations in
this design are explored and examples of different designs for fat metabolism
from animal physiology are included to illustrate these limitations. Various
means of manipulating fat metabolism are discussed with special emphasis on
exercise, training, growth hormone (GH) physiology and GH administration. It is
concluded that fat stores, non-esterified fatty acids (NEFAs) availability and
enzymes for fat oxidation can be increased substantially. However, it is almost
impossible to increase fat oxidation during endurance exercise at higher
intensities. It seems that, for some reason, the human being is far from
optimally designed for fat oxidation during exercise. Acute GH administration
has several unexpected effects on fat and carbohydrate metabolism during aerobic
exercise, and future research in this area is likely to provide valuable
information with respect to GH physiology and the regulation of fat and
carbohydrate metabolism during aerobic exercise.
PMID: 15043630 [PubMed]
24: Br J Sports Med. 2004 Apr;38(2):186-90.
Effects of exercise on the physical condition of college rugby players during
summer training camp.
Mashiko T, Umeda T, Nakaji S, Sugawara K.
Department of Health and Physical Education, National Defense Medical College,
Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
OBJECTIVES: To determine the effects of exercise training on physical condition
in 25 college rugby players during a summer training camp, and to compare these
variables by the different players' positions. METHODS: Changes in body
composition parameters and blood biochemistry were examined before and after a
summer training camp. RESULTS: Body weight and percentage body fat did not
change significantly during the camp. There were significant decreases in levels
of serum total cholesterol, triglycerides, phosphate, uric acid, and
immunoglobulin G and M. In contrast, there were significant increases in levels
of serum potassium, markers of renal, hepatic, and muscular damage (BUN, GOT,
GPT, LDH, CK), and complement C4. Comparison of the changes in biochemical
parameters between rugby players playing in different positions showed a
significant increase in serum albumin level in the forwards, and significant
decreases in serum triglyceride and sodium levels in the backs. The magnitude of
change in serum LDH during the camp was significantly greater (p<0.05) for the
forwards than for the backs. CONCLUSIONS: These data suggest that, in rugby
players attending a 20 day camp, exercise training resulted in muscular damage,
loss of electrolytes due to sweating, and changes in immune function. Backs
exhibited a higher rate of fat metabolism and loss of electrolytes than
forwards, possibly because they did more running during the camp. In contrast,
forwards experienced more physical contact, performed more physically strenuous
exercise, and exhibited higher levels of muscular damage and tissue protein
degradation.
PMID: 15039257 [PubMed]
25: Int J Obes Relat Metab Disord. 2004 Mar 23 [Epub ahead of print]
Relationship between changes in food group variety, dietary intake, and weight
during obesity treatment.
Raynor HA, Jeffery RW, Tate DF, Wing RR.
1Department of Psychiatry and Human Behavior, Brown University, The Miriam
Hospital, Providence, RI, USA.
BACKGROUND:: Experimental studies show diets with greater variety in
energy-dense foods increase consumption and body weight. Reducing variety in
energy-dense food groups may decrease energy and dietary fat intake, promoting
weight loss. OBJECTIVE:: This study examined changes in food group variety
during obesity treatment and the relation between changes in food group variety,
dietary intake, and weight. DESIGN:: Overweight men and women (n=202) were
randomly assigned to one of two standard behavioral treatments with varying
exercise prescriptions (exercise level of 4186 kJ/week (1000 kcal/week) or 10465
kJ/week (2500 kcal/week)), but received the same diet. Complete measures were
obtained from 122 participants, of which 70 (58%) were female, with a mean body
mass index of 31.3 kg/m(2) (s.d.=2.5). MEASUREMENTS:: Food group variety and
diet composition were assessed at 0, 6, and 18 months from food-frequency
questionnaires. Food group variety was calculated as percent of foods consumed
on a weekly basis within a food group, irrespective of servings consumed.
RESULTS:: Participants reported increased variety (P 0.10) affect Warner-Bratzler shear force (WBSF), collagen
amount (OH-PRO) or cross-linking (HP), temperature, or pH. Steaks from WxL aged
14 d postmortem had lower (P < 0.05) WBSF values than L (W were intermediate).
Cooking time was longer (P < 0.01) in W and WxL than in L; however, breed did
not affect (P > 0.10) cooking loss. Cooking time was not influenced by diet, but
steaks from cattle fed 6% sunflower oil had lower (P < 0.05) cooking losses.
Temperature decreased more (P < 0.05) rapidly, and pH more slowly (P < 0.05), in
W and WxL than L in the first 24 h postmortem. Limousin steaks were lighter
(higher L*) and more yellow (higher b*) in color than steaks from W and WxL (P <
0.05). The control diet (no oil added) resulted in steaks that were lighter (P <
0.05) than the treatment diet (6% added sunflower oil). Neither breed nor diet
affected (P > 0.10) OH-PRO or HP concentration. The results of this study
indicate that biological type differences may not be as great in the ST as in
longissimus muscle; thus, to increase tenderness in ST, emphasis may need to be
placed on processing and cooking techniques rather than genetic selection.
PMID: 15032434 [PubMed]
29: Circulation. 2004 Mar 30;109(12):1550-7. Epub 2004 Mar 15.
Fatty acid translocase/CD36 deficiency does not energetically or functionally
compromise hearts before or after ischemia.
Kuang M, Febbraio M, Wagg C, Lopaschuk GD, Dyck JR.
Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine,
University of Alberta, Edmonton, Alberta, Canada.
BACKGROUND: Evidence from humans suggests that fatty acid translocase (FAT)/CD36
deficiency can lead to functionally and/or energetically compromised hearts, but
the data are equivocal, and the subject remains controversial. In this report we
assessed the contribution of FAT/CD36 to overall fatty acid oxidation rates in
the intact heart and determined the effect of FAT/CD36 on energy metabolism
during reperfusion of ischemic hearts. METHODS AND RESULTS: Isolated working
hearts from wild-type and FAT/CD36-knockout (KO) mice were perfused with
Krebs-Henseleit solution containing 0.4 or 1.2 mmol/L [U-3H]palmitate, 5 mmol/L
[U-14C]glucose, 2.5 mmol/L calcium, and 100 microU/mL insulin at a preload
pressure of 11.5 mm Hg and afterload pressure of 50 mm Hg. Hearts were
aerobically perfused for 30 minutes or aerobically perfused for 30 minutes,
followed by 18 minutes of global no-flow ischemia and 40 minutes of aerobic
reperfusion. Rates of fatty acid oxidation in FAT/CD36-KO hearts were
significantly lower than in wild-type hearts at both concentrations of palmitate
(0.4 or 1.2 mmol/L). In addition, hearts from FAT/CD36-KO mice displayed a
compensatory increase in glucose oxidation rates. On aerobic reperfusion after
ischemia, cardiac work of FAT/CD36-KO hearts recovered to the same extent as
wild-type hearts. CONCLUSIONS: FAT/CD36-deficient hearts are not energetically
or functionally compromised and are not more sensitive to ischemic injury
because glucose oxidation can compensate for the loss of fatty acid-derived ATP.
PMID: 15023869 [PubMed]
30: Asia Pac J Clin Nutr. 2003;12 Suppl:S52.
High dairy-protein versus high mixed-protein energy restricted diets - the
effect on bone turnover and calcium excretion in overweight adults.
Bowen J, Noakes M, Clifton P.
Clinical Research Unit, CSIRO Health Sciences and Nutrition, PO Box 10041,
Adelaide, SA 5000.
Background - A moderate exchange of some dietary carbohydrate for protein
appears to have metabolic and weight loss advantages in human studies. This
dietary strategy raises safety concerns for bone health. The impact of dietary
calcium in high protein diets on bone turnover has not been investigated.
Objective - This study examined the effect of protein source and calcium content
in high protein, energy restricted diets on calcium excretion and bone
metabolism in 50 overweight adults (BMI 33.4 +/- 2.1 kg/m(2)). Design - The
parallel study consisted of a 12-week energy restriction phase followed by a
four-week energy balance phase. Subjects were randomised to one of two
isoenergetic (5.5 MJ/d, 34% energy from protein, 41% from carbohydrate and 24%
from fat) diets; high dairy protein (DP, 2400mg Ca/d) or high mixed protein (MP,
500mg Ca/d). Outcomes - Energy restriction was the primary determinant of weight
loss (-9.7 +/- 3.8 kg, P<0.01) with no significant effect of protein source.
Twenty-four hour calcium excretion decreased during both interventions (-1.09
+/- 0.23 mmol/day, P<0.009). By week 16 the MP diet had a 40% larger increase in
deoxypyridinoline (a bone turnover marker) compared to the DP diet (P=0.008).
Osteocalcin (a marker of bone formation) increased from week zero to 16 in the
MP diet only (+2.22 ng/ml P=0.001). Conclusions - Overall, the DP diet has a
modest advantage over MP diet by reducing the accelerated bone turnover
associated with weight loss.
PMID: 15023671 [PubMed]
31: Asia Pac J Clin Nutr. 2003;12 Suppl:S10.
Dietary approaches for weight loss with increased fruit, vegetables and dairy.
Booth AO, Nowsen CA, Worsley T, Margerison C, Jorna MK.
School of Health Sciences, Deakin University, Burwood, VIC 3215.
Objective - To assess the consumption of fruit, vegetables and non-fat dairy
products of subjects in a weight loss study where strategies were used to
increase intakes. Design - Subjects were randomised to one of two diet and
exercise weight loss programs for 12 weeks (n=40). The WELL diet (a Dietary
Approaches to Stop Hypertension (DASH) type diet with a weight loss focus)
included daily targets of four serves of fruits, four serves of vegetables and
three serves of no fat dairy. The National Heart Foundation's (NHF) 'Healthy
Weight Guide' diet included general advice to increase fruit and vegetable
consumption but no specific targets. Subjects were visited or phoned
fortnightly. They received group weight loss feedback as well as a personalized
program that included lifestyle advice, feedback and goal setting. A food group
counter recorded servings of fruit, vegetables and dairy products on three
consecutive days of each week. Results of the first eight weeks are reported.
Results - At week 8, number of serves/day of targeted foods were greater for the
WELL diet than the NHF diet (mean difference+/-SEM): Fruit: 1.5+/-0.3,
vegetables: 1.5+/-0.2, dairy: 1.3+/-0.1 serves/day (all P<0.01). Vegetables
serves/day (mean+/-SEM) on the WELL diet increased from week two to week eight
(week two: 3.3+/-0.2, week eight: 4.1+/-0.4 serves/day (P<0.05)). Daily fruit
intake remained above target (week two: 4.7+/-0.2, week eight: 4.8+/-0.1
serves/day). Daily dairy intake remained below target (week two: 2.7+/-0.2, week
eight: 2.8 +/-0.2serves/day). Conclusions - Changing dietary patterns may
require different adjustment periods depending on the food type. Increasing
fruit intake can be implemented quickly, whereas it takes a longer time to
increase vegetable intake. Providing specific dietary targets appears to promote
greater adherence to guidelines than general advice to increase intakes alone.
PMID: 15023596 [PubMed]
32: Asia Pac J Clin Nutr. 2003;12 Suppl:S9.
The effect of protein source (dairy vs mixed) in high protein, energy restricted
diets on body composition, vascular health and metabolic markers in overweight
adults.
Bowen J, Noakes M, Clifton P.
Clinical Research Unit, CSIRO Health Sciences and Nutrition, PO Box 10041,
Adelaide, SA.
Background - An increase in the protein/carbohydrate ratio in low calorie diets
has been linked with improved metabolic profile. It is unclear if the source of
dietary protein exerts any affects. There is limited evidence that high calcium
diets may facilitate body fat loss. Objective - This study examined whether a
high dairy protein/calcium diet versus a mixed protein/low calcium diet affected
weight loss and cardiovascular and liver function markers. Design - The parallel
study consisted of a 12-week phase energy restriction followed by a 4-week
energy balance phase. Fifty adults (BMI 33.4 +/- 2.1 kg/m(2)) followed
isocaloric diets (5.5MJ/day, 34% protein, 41% carbohydrate, 24% fat) high in
dairy (DP, 2400mg Ca/d) or mixed protein (MP, 500mg Ca/d). Body composition,
glycemic control, serum lipids, blood pressure and markers of vascular and liver
function were measured throughout the study. Outcomes - There was no effect of
protein source on net weight loss or body composition (-9.7 +/- 3.8kg, P=0.8).
Prior to weight loss, glycemic response to DP or MP test meals was 30% lower in
subjects on the DP diet. Fasting total and LDL-cholesterol, triglycerides,
insulin and blood pressure decreased after weight
loss(-0.41+/-0.07mmol/L,-0.36+/-0.1mmol/L,-0.23+/-0.06 mmol/L,-1.4+/-0.6mU/L,
-9.4/-2.5mmHg P<0.01, respectively) independent of protein source. There was an
improvement in some markers of liver function as well as markers of vascular
function (GTT, AST, PAI, sICAM, tPA) with weight loss (-20.1+/-4.1%,-11.2+/-17%,
-15.2+/-7.3%,-6.9+/-2.2%,+25.9+/-6.2%, respectively P<0.01). Conclusions - Both
diets resulted in improvements in cardiovascular risk markers and liver
function. Neither protein source nor dietary calcium significantly affected
weight loss or body composition. The DP test meal resulted in a slightly more
favourable glucose response.
PMID: 15023595 [PubMed]
33: Asia Pac J Clin Nutr. 2003;12 Suppl:S8.
Novel treatments for Obesity.
Ludwig DS.
Department of Medicine, Children's Hospital Boston, MA, USA.
Background - Excessive fat consumption is commonly believed to cause obesity
and, for this reason, conventional approaches to weight loss have focused on
decreasing dietary fat. However, the relationship between dietary fat and
adiposity has been questioned for several reasons: 1) weight loss on low-fat
diets is characteristically modest in nature; 2) prospective epidemiological
studies have not consistently found that individuals eating the most fat are
heavier than those eating the least fat; and 3) obesity prevalence has risen
markedly since the 1970s in the US despite a significant decrease in fat
consumption as a percent of total energy. As dietary fat has decreased,
carbohydrate consumption has increased in a compensatory fashion, and most of
this increase has been in the form of refined starchy food and concentrated
sugar that are high in glycemic index (GI) and/or glycemic load (GL). Review -
Physiological studies demonstrate that consumption of high GI/GL meals induce a
sequence of hormonal changes that limit availability of metabolic fuels in the
post-prandial period and cause overeating. Short-term feeding studies
consistently show less satiety or greater voluntary energy intake after
consumption of high compared to low GI meals. Several intermediate-term clinical
trials found greater weight loss among overweight individuals on low compared to
low GI diets. A recent study from our group found significantly greater weight
and fat mass decrease among obese adolescents consuming a reduced GL compared to
a reduced fat diet for 12 months. Animal studies support a role for GI in body
weight regulation. Moreover, GI and GL appear to affect risk for diabetes and
heart disease after controlling for body weight. Conclusions - Reduction in
GI/GL comprises a novel and exciting approach to the prevention and treatment of
obesity and related complications. A low GI/GL diet may be an ideal compromise
between low fat diets at one end of the spectrum, and very low carbohydrate
diets at the other. Long-term, large-scale studies of such diets should assume a
high public health priority.
PMID: 15023593 [PubMed]
34: Asia Pac J Clin Nutr. 2003;12 Suppl:S4.
Diet and development of the insulin resistance syndrome.
Ludwig DS.
Department of Medicine, Children's Hospital Boston, MA,SA.
Background -Insulin influences a large number of physiological functions in a
variety of organs and tissues. From a broad perspective, insulin resistance
provides the body with the ability to regulate the actions of this potent
anabolic hormone in a highly discrete fashion. Many patho-physiological factors
can alter the functions of insulin at one or more sites, potentially conferring
biological benefit. However, insulin resistance and compensatory
hyperinsulinemia in the setting of central adiposity adversely affects important
diabetes and cardiovascular disease risk factors - namely glucose tolerance,
blood pressure, serum lipids, coagulation tendency, chronic inflammation and
perhaps oxidative stress - that together comprise the insulin resistance
syndrome (IRS). Review - Dietary factors have increasingly been recognized as
important determinants of insulin resistance and, by implication, development of
the IRS. Though low fat/high carbohydrate diets have been traditionally
recommended to reduce risk for diabetes and cardiovascular disease, recent
research has suggested that such diets may actually increase risk for IRS among
susceptible individuals. On balance, macronutrient quantity may be less
important in this regard than nutrient quality. Whereas saturated and
trans-fatty acids increase insulin resistance, mono and poly-unsaturated fats
decrease resistance and offer protection against disease. Similarly, some types
of carbohydrate (refined starch, concentrated sugar) promote, and other types
(high fiber, low glycemic index) protect against IRS. Beyond macronutrients,
specific food groups have become the subject of increasing interest.
Observational and interventional studies suggest that dairy products, including
full fat versions, lower risk for IRS, an effect that might be mediated by
intrinsic compounds in dairy (e.g calcium) or by displacement of less healthful
foods (e.g soft drinks) from the diet. Preliminary studies suggest that certain
micronutrients might also influence risk. Conclusions - Among modifiable factors
including weight loss and exercise, dietary composition appears to have an
important effect on development of IRS. The available evidence suggests that
IRS, and therefore diabetes and cardiovascular disease, can be prevented by a
high fiber/low glycemic index diet containing dairy products and a higher amount
of unsaturated fats than currently recommended.
PMID: 15023589 [PubMed]
35: Fertil Steril. 2004 Mar;81 Suppl 1:792-7.
Oxidative stress indices in seminal plasma, as measured by the
thermochemiluminescence assay, correlate with sperm parameters.
Lissak A, Wiener-Megnazi Z, Reznick AZ, Shnizer S, Ishai D, Grach B,
Lahav-Baratz S, Shiloh H, Koifman M, Dirnfeld M.
IVF Unit, Department of Obstetrics and Gynecology, Carmel Medical Center, 7
Michal Street, Haifa, Israel.
OBJECTIVE: To examine the effect of oxidation of proteins and lipids, as
measured by a novel thermochemiluminescence (TCL) analyzer, and to evaluate the
correlation between TCL indices in seminal plasma and sperm parameters. DESIGN:
Experimental and prospective clinical studies. SETTING: An infertility unit.
PATIENT(S): One hundred forty-eight men undergoing semen analysis.
INTERVENTION(S): Bovine serum albumin (BSA) and linolenic acid were oxidized and
tested by TCL, protein carbonyls, and conjugated dienes assays. All participants
underwent semen analysis. Seminal plasma was tested by TCL and conjugated
dienes. MAIN OUTCOME MEASURE(S): Thermochemiluminescence indices before and
after oxidation of BSA and linolenic acid, compared with protein carbonyl and
conjugated dienes indices. Correlation between semen parameters and TCL and
conjugated dienes indices in seminal plasma. RESULT(S): Oxidation of BSA and
linolenic acid was marked by characteristic changes in their TCL curve pattern
and an increase in the levels of protein carbonyls and conjugated dienes. Among
125 sperm-containing semen samples, the TCL curve exhibited two patterns: a
positive relative ratio curve (group A, 87 patients) and a negative relative
ratio curve (group B, 38 patients). Sperm concentration was lower and total
motile sperm and rapid motile sperm were fewer in group B. A significant
correlation was found between TCL indices, conjugated dienes, and sperm quality
in group B. CONCLUSION(S): Oxidation affects TCL curve pattern of proteins and
lipids in a characteristic manner. Thermochemiluminescence indices in seminal
plasma closely correlate with sperm characteristics among patients with sperm
disturbances, and it might serve as a tool in the evaluation, treatment, and
monitoring of subfertile men.
PMID: 15019811 [PubMed]
36: Pediatr Diabetes. 2000 Mar;1(1):23-33.
Recent advances in the treatment of childhood obesity.
Suskind R, Blecker U, Udall Jr J, Von Almen T, Schumacher H, Carlisle L, Sothern
M.
The Chicago Medical School, North Chicago, IL, USA.
The rapid increase in the prevalence of obesity in the last decade indicates a
need for effective treatment programs. We conducted a short-term,
repeated-measures, clinical-outcome trial in three groups of children and
adolescents in two different locations. Two cohorts (n=34) were enrolled in a
36-wk multi-disciplinary weight-management program at the Children's Hospital of
New Orleans. One cohort (n=16) was enrolled in a similar intervention at the
General Clinical Research Center (GCRC) at the Medical Center of Louisiana for a
10-wk summer weight-loss program. Subjects were offered a protein-sparing
modified fast (PSMF) diet (600-800 kcal/d; 2 g protein/kg body weight), followed
by a balanced hypocaloric diet, and they participated in behavior-modification
sessions and a moderate-intensity (45-55% volume of oxygen consumed at maximal
effort [VO(2)max]), progressive exercise program. The following parameters were
examined at baseline, 10 wk, and 36 wk (cohort 1 only): Weight, height,
percentage of ideal body weight (%IBW), relative body fat (%fat), fat free body
(FFB) mass, estimated VO(2)max mL/kg min(BW) [adjusted for body weight]), blood
chemistries, lipid profiles (total cholesterol [TC], triglycerides [TG],
low-density lipoprotein [LDL], high-density lipoprotein [HDL], and insulin-like
growth factor-1 [IGF-1]). All three groups experienced significant decreases in
weight, %IBW and %fat at 10 wk. The weight loss was maintained at 26 wk in
cohorts 1 and 2, and at 36 wk in cohort 1. There were no significant decreases
in height velocity during the study. In addition, measures of estimated VO(2)max
mL/kg/min(BW) and IGF-1 parameters were significantly greater at 10 wk compared
to baseline. Measures of TC, TG, and LDL were significantly lower at 10 wk, with
no significant changes noted in HDL. We conclude that a multi-disciplinary
weight-management program, including PSMF, behavior modification, and exercise,
provides an effective method of treatment for obesity in children and
adolescents. Long-term, randomized, and controlled clinical trials are needed to
confirm the results of this preliminary, short-term observation.
PMID: 15016239 [PubMed]
37: Pediatr Diabetes. 2000 Jun;1(2):61-5.
Changes in body composition after a 12-wk aerobic exercise program in obese
boys.
DeStefano RA, Caprio S, Fahey JT, Tamborlane WV, Goldberg B.
Section of Cardiology, Department of Pediatrics and the Children's Clinical
Research Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Previous studies have shown that vigorous aerobic training programs for obese
children result in minimal weight changes, and concluded that they may not be
beneficial. Weight change alone may not detect important beneficial changes in
body composition associated with vigorous training in these children. Fifteen
obese boys (aged 9-12 yr, body mass index (BMI) 31.8+/-6.5, average percent body
fat (%BF) 41+/-4.2) underwent a supervised aerobic and resistance training
program (12 wk, 2 days/wk for 30 min/session), to investigate the effects on
weight and body composition. After the 3-month training period, weight loss
averaged only 1.5+/-1.0 kg (not significant), but total body fat decreased by
4.1+/-1.8 kg (p<0.05) and fat-free mass (FFM) increased by 2.6+/-1.1 kg (p<0.05)
based on hydrostatic weighing. As a result, %BF fell by 10% (p<0.01). There was
a 5.8+/-2.8 mL/kg/min (p<0.05) increase in peak volume of oxygen uptake (VO(2)),
along with a 248+/-120 kcal/d (p<0.05) increase in resting energy expenditure
(REE). Activity questionnaires showed a significant increase in high intensity
recreational activities (6.5+/-1.5 vs 3.5+/-0.5 h physical activity/wk; p<0.01)
in the home and a significant decrease in low intensity activities (7+/-2.0 vs
12+/-3.5 h TV viewing/wk; p<0.01). Conclusions: Vigorous supervised aerobic
training in obese boys has beneficial effects on body composition, fitness and
leisure time activities that are not apparent by measurement of changes in body
weight alone.
PMID: 15016230 [PubMed]
38: Metabolism. 2004 Mar;53(3):388-96.
The hyperinsulinemic amino acid clamp increases whole-body protein synthesis in
young subjects.
Chevalier S, Gougeon R, Kreisman SH, Cassis C, Morais JA.
McGill Nutrition and Food Science Centre, Montreal, Quebec, Canada.
We propose that hyperinsulinemia stimulates protein synthesis when
postabsorptive plasma amino acid (AA) concentrations are maintained. During a
euglycemic hyperinsulinemic clamp, many AA, notably the branched-chain amino
acids (BCAA), decline markedly. Therefore, we tested whether individual plasma
AA could be maintained within the range of postabsorptive concentrations to
assess the effects of insulin, infused at 40 mU/m(2) x min on whole-body protein
and glucose metabolism, using [1-(13)C]-leucine and [3-(3)H]-glucose
methodology. Validation studies of background [(13)C] enrichment and breath
(13)CO(2) recovery factors were performed in a subset of 6 subjects. In 10
healthy, young men, infusion rates of an AA solution were based on fluorometric
determinations of total BCAA every 5 minutes. All 21 plasma AA remained in the
target range; 15, including the BCAA, alanine, and glycine were within 13% of
baseline, and only 6 (Thr, His, Arg, Asn, Cit, Tyr) varied more (18% to 42%).
Notably, both leucine flux and nonoxidative leucine R(d) (protein synthesis)
increased with insulin (2.36 +/- 0.06 to 2.81 +/- 0.10 and 1.79 +/- 0.05 to 2.18
+/- 0.10 micromol/kg fat-free mass (FFM) x min, respectively; P <.0005) while
leucine oxidation only tended to increase (P =.05) and endogenous leucine R(a)
(protein breakdown) decreased by 18% (2.36 +/- 0.06 to 1.94 +/- 0.09 micromol/kg
FFM x min; P <.0005), resulting in a marked elevation of net protein synthesis
(-0.57 +/- 0.02 to 0.24 +/- 0.02 micromol/kg FFM x min; P <.0000001). Thus, in
vivo protein anabolism was induced when maintaining postabsorptive plasma amino
acid concentrations during hyperinsulinemia through a suppression of whole-body
protein breakdown, no significant change in oxidation and an elevation of
synthesis compared with postabsorptive conditions.
PMID: 15015153 [PubMed]
39: MMW Fortschr Med. 2003 Apr 28;145 Spec No 1:28-32.
[In Process Citation]
[Article in German]
Weber K, Heiken H, Stoll M, Schmidt RE, Behrens G.
Abteilung Klinische Immunologie, Medizinische Hochschule Hannover.
weber-r.klaus@mh-hannover.de
A common problem seen with the long-term use of highly active antiretroviral
therapy (HAART) is the HIV-associated lipodystrophy syndrome. Clinical signs
include a loss of peripheral subcutaneous fatty tissue, an increase in visceral
or local fat, and altered glucose and lipid metabolism. The physical changes
frequently impair quality of life, and the patient's adherence to treatment
regimens. Metabolic changes may possibly represent cardiovascular risks with
incalculable consequences over the long term. Although the lipodystrophy
syndrome was first described in 1998. It still lacks a definition. So far,
therapeutic strategies have remained ineffective or have had only limited
success. Proposed treatments include general recommendations (diet, physical
exercise, etc.), changing the antiretroviral therapy, and treatment with
metabolically active medication.
PMID: 15011581 [PubMed]
40: Br J Plast Surg. 2004 Apr;57(3):190-4.
Comment in:
Br J Plast Surg. 2004 Apr;57(3):189.
Effect of liposuction on insulin resistance and vascular inflammatory markers in
obese women.
Giugliano G, Nicoletti G, Grella E, Giugliano F, Esposito K, Scuderi N, D'Andrea
F.
Chair of Plastic and Reconstructive Surgery, Second University of Naples,
Naples, Italy. dario.giugliano@unina2.it
Liposuction is one of the more common elective surgical procedures in the US and
is supposed to be on the increase. There are no reported studies specifically
addressing the metabolic sequelae of liposuction in obesity. The aim of the
present study was to investigate the role of large-volume liposuction on insulin
resistance and circulating inflammatory markers in obese people. Thirty healthy
premenopausal obese (body mass index (BMI) from 30 to 45) and 30 age-matched
normal weight (BMI<25) women were studied. In obese women, insulin sensitivity,
as measured by the Homeostasis Model Assessment (HOMA=fasting plasma glucose x
fasting serum insulin divided by 25), as well as serum adiponectin, the novel
adipocytokine with insulin sensitising properties, were significantly lower, as
compared with nonobese women (p<0.01), indicating insulin resistance; on the
contrary, serum concentrations of the proinflammatory cytokines IL-6, IL-18 and
TNF-alpha, as well as the sensitive marker of inflammation C-reactive protein,
were significantly higher (p<0.01). All obese women were submitted to a single
large volume liposuction (superwet technique): the mean aspirate volume was 3540
ml (range 2550-4670), corresponding to a net lipid loss of 2.7+/-0.7 kg
(mean+/-SD). After six months of stable body weight after liposuction, women
were less insulin resistant (p<0.05), had reduced concentrations of IL-6, IL-18,
TNF-alpha and CRP (p<0.05-0.02), and increased serum levels of adiponectin
(p<0.02) and HDL-cholesterol (p<0.05). There was a significant correlation
between the amount of fat aspirate and changes in HOMA (r=0.28, p<0.05),
TNF-alpha (r=0.31, p<0.02), and adiponectin (r=-0.34, p<0.02), as well as
between the decrease in TNF-alpha and the increase in adiponectin after the
surgical procedure (r=-0.45, p<0.01). Our study demonstrates that liposuction is
safe and free of metabolic sequelae in obese women, pending a careful screening
of the patient. Moreover, it is associated with amelioration of insulin
resistance and reduced circulating markers of vascular inflammation which may
help obese subjects to reduce their cardiovascular risk.
PMID: 15006519 [PubMed]
41: Am J Physiol Regul Integr Comp Physiol. 2004 Apr;286(4):R734-9.
Leptin prevents obesity induced by a high-fat diet after diet-induced weight
loss in the marsupial S. crassicaudata.
Wittert GA, Turnbull H, Hope P, Morley JE, Horowitz M.
Department of Medicine, Royal Adelaide Hospital, Adelaide SA 5000, Australia.
gary.wittert@adelaide.edu.au
The aims of this study were to determine in the marsupial Sminthopsis
crassicaudata, the effects of leptin on food intake, body weight, tail width (a
reflection of fat stores), and leptin mRNA, after caloric restriction followed
by refeeding ad libitum with either a standard or high-fat preferred diet. S.
crassicaudata (n = 32), were fed standard laboratory diet (LabD; 1.01 kcal/g,
20% fat) ad libitum fo 3 days. On days 4-10, animals received LabD at 75% of
basal intake and then (days 11-25) were fed either LabD or a choice of LabD and
mealworms (MW; 2.99 kcal/g, 30% fat); during this time, half the animals (n = 8)
in each group received either leptin (2.5 mg/kg) or PBS intraperitoneally two
times daily. On day 26, animals were killed and fat was removed for assay of
leptin mRNA. At baseline, body weight, tail width, and food intake were similar
in each group. After caloric restriction, body weight (P < 0.001) and tail width
(P < 0.001) decreased. On return to ad libitum feeding in the PBS-treated
animals, body weight and tail width returned to baseline in the LabD-fed animals
(P < 0.001) and increased above baseline in the MW-fed animals (P < 0.001). In
the LabD groups, tail width (P < 0.001) and body weight (P < 0.001) decreased
after leptin compared with PBS. In the MW groups, the increase in tail width (P
< 0.001) and body weight (P = 0.001) were attenuated after leptin compared with
PBS. The expression of leptin mRNA in groups fed MW were greater in PBS than in
leptin-treated animals (P < 0.05). Therefore, after diet-induced weight loss,
leptin prevents a gain in fat mass in S. crassicaudata; this has potential
implications for the therapeutic use of leptin.
PMID: 15003944 [PubMed]
42: J Clin Endocrinol Metab. 2004 Mar;89(3):1301-11.
Dissociation between fat-induced in vivo insulin resistance and proximal insulin
signaling in skeletal muscle in men at risk for type 2 diabetes.
Storgaard H, Jensen CB, Bjornholm M, Song XM, Madsbad S, Zierath JR, Vaag AA.
Department of Endocrinology and Clinical Research Unit, Hvidovre Hospital,
University of Copenhagen, DK-2650 Hvidovre, Denmark. hstorgaard@dadlnet.dk
The effect of short- (2 h) and long-term (24 h) low-grade Intralipid infusion on
whole-body insulin action, cellular glucose metabolism, and proximal components
of the insulin signal transduction cascade was studied in seven obese male
glucose intolerant first degree relatives of type 2 diabetic patients [impaired
glucose tolerance (IGT) relatives] and eight matched control subjects. Indirect
calorimetry and excision of vastus lateralis skeletal muscle biopsies were
performed before and during hyperinsulinemic euglycemic clamps combined with
3[(3)H]glucose. Clamps were performed after 0, 2, or 24 h Intralipid infusion
(0.4 ml.kg(-1).min(-1)). Insulin-stimulated glucose disposal decreased
approximately 25% after short- and long-term fat infusion in both IGT relatives
and controls. Glucose oxidation decreased and lipid oxidation increased after
both short- and long-term fat infusion in both groups. Insulin-stimulated
glucose oxidation was higher after long-term as compared with short-term fat
infusion in control subjects. Short- or long-term infusion did not affect the
absolute values of basal or insulin-stimulated insulin receptor substrate-1
tyrosine phosphorylation, tyrosine-associated phosphoinositide 3-kinase (PI
3-kinase) activity, insulin receptor substrate-1-associated PI 3-kinase
activity, or Akt serine phosphorylation in IGT relatives or matched controls. In
fact, a paradoxical increase in both basal and insulin-stimulated PI 3-kinase
activity was noted in the total study population after both short- and long-term
fat infusion. Short- and long-term low-grade Intralipid infusion-induced (or
enhanced) whole-body insulin resistance and impaired glucose metabolism in IGT
relatives and matched control subjects. The fat-induced metabolic changes were
not explained by impairment of the proximal insulin signaling transduction in
skeletal muscle.
Publication Types:
Clinical Trial
PMID: 15001626 [PubMed]
43: Eur J Nutr. 2004 Feb;43(1):2-6. Epub 2004 Jan 06.
Plasma antioxidants and lipid oxidation after submaximal resistance exercise in
men.
Ramel A, Wagner KH, Elmadfa I.
Unit for Nutrition Research, University of Iceland, Eiriksgata 29, 101,
Reykjavik, Iceland. ramel@hi.is
BACKGROUND: An increased generation of reactive oxygen species occurs during
exercise. THE AIM OF THE STUDY: We investigated whether changes in plasma
antioxidants and lipid oxidation products after submaximal resistance exercise
are detectable, and whether training status has any effect on changes. METHODS:
Seven resistance trained (RT, 31.3 +/- 10.2 yrs) and ten non-resistance trained
male subjects (NRT, 28.2 +/- 3.9 yrs) performed a submaximal resistance exercise
circuit (10 different exercises, 75% of 1-repetition maximum, 18.6 +/- 1.1
minutes). Blood samples were taken before and immediately after exercise. Plasma
antioxidants (AO), lipid oxidation products malondialdehyde (MDA) and conjugated
dienes (CD) were measured using HPLC and/or photometric detection. Groups were
compared using the Mann-Whitney U test, the exercise effect was tested using the
Wilcoxon signed ranks test. P < 0.05 was regarded as significant. RESULTS:
alpha-Tocopherol, gamma-tocopherol, beta-carotene, lycopene, ascorbic acid,MDA
and CD concentrations did not differ between groups at rest. There was a similar
increase of fat soluble plasma AO in both groups after exercise, but not
ascorbic acid. MDA increased also in both groups after exercise, but CD
increased only in NRT. CONCLUSION: There is no difference in plasma AO and lipid
oxidation products in RT and NRT at rest. After short time resistance exercise
there is a mobilization of fat soluble AO. Despite mobilization of AO, oxidative
stress occurs during submaximal resistance exercise, which is indicated by
increased MDA and CD concentrations. As exercise induced an increase of CD only
in NRT, it seems that regular resistance training partly prevents lipid
peroxidation during exercise.
PMID: 14991263 [PubMed]
44: J Nutr. 2004 Mar;134(3):586-91.
High-protein, low-fat diets are effective for weight loss and favorably alter
biomarkers in healthy adults.
Johnston CS, Tjonn SL, Swan PD.
Department of Nutrition, Arizona State University, Mesa, AZ 85212, USA.
carol.johnston@asu.edu
Although popular and effective for weight loss, low-carbohydrate, high-protein,
high-fat (Atkins) diets have been associated with adverse changes in blood and
renal biomarkers. High-protein diets low in fat may represent an equally
appealing diet plan but promote a more healthful weight loss. Healthy adults (n
= 20) were randomly assigned to 1 of 2 low-fat (<30% energy), energy-restricted
groups: high-protein (30% energy) or high-carbohydrate (60% energy); 24-h
intakes were strictly controlled during the 6-wk trial. One subject from each
group did not complete the trial due to out-of-state travel; two subjects in the
high-carbohydrate group withdrew from the trial due to extreme hunger. Body
composition and metabolic indices were assessed pre- and post-trial. Both diets
were equally effective at reducing body weight (-6%, P < 0.05) and fat mass (-9
to -11%, P < 0.05); however, subjects consuming the high-protein diet reported
more satisfaction and less hunger in mo 1 of the trial. Both diets significantly
lowered total cholesterol (-10 to -12%), insulin (-25%), and uric acid (-22 to
-30%) concentrations in blood from fasting subjects. Urinary calcium excretion
increased 42% in subjects consuming the high-protein diet, mirroring the 50%
increase in dietary calcium with consumption of this diet; thus, apparent
calcium balance was not adversely affected. Creatinine clearance was not altered
by diet treatments, and nitrogen balance was more positive in subjects consuming
the high-protein diet vs. the high-carbohydrate diet (3.9 +/- 1.4 and 0.7 +/-
1.7 g N/d, respectively, P < 0.05). Thus, low-fat, energy-restricted diets of
varying protein content (15 or 30% energy) promoted healthful weight loss, but
diet satisfaction was greater in those consuming the high-protein diet.
PMID: 14988451 [PubMed]
45: J Nutr. 2004 Mar;134(3):568-73.
A high dairy protein, high-calcium diet minimizes bone turnover in overweight
adults during weight loss.
Bowen J, Noakes M, Clifton PM.
CSIRO Health Sciences and Nutrition, Adelaide, South Australia, Australia, 5000.
Weight loss induces bone resorption and this can be attenuated by calcium
supplementation. Protein-rich diets were recently associated with favorable
effects on bone density, although this remains controversial. We hypothesized
that a diet high in calcium and protein would minimize bone resorption during
weight loss compared with a lower calcium, protein-rich diet. The effects of
dietary calcium in high protein diets on calcium excretion and bone metabolism
were examined in overweight adults (n = 50, BMI 33.4 +/- 2.1 kg/m(2)) during 12
wk of energy restriction followed by 4 wk of energy balance. Subjects were
randomly assigned to isoenergetic diets (5.5 MJ/d, 34% energy from protein, 41%
carbohydrate, 24% fat) high in either dairy protein (DP, 2400 mg Ca/d) or mixed
protein sources (MP, 500 mg Ca/d). During energy restriction, weight loss was
10% (-9.7 +/- 3.8 kg, P < 0.01), and 24-h urinary calcium excretion decreased
independently of diet (-1.09 +/- 0.23 mmol/d, P < 0.01). By wk 16, the MP diet
group had a 40% greater increase in deoxypyridinoline (bone resorption marker)
than the DP diet group (P = 0.008). Osteocalcin (bone formation marker)
increased from wk 0 to 16 in only the MP diet group [+2.16 +/- 0.63 micro g/L
(+0.63 +/- 0.11nmol/L), P = 0.001]. In conclusion, weight loss was associated
with increased bone resorption, yet the DP diet had a modest advantage over the
MP diet by minimizing overall turnover. Combined with reduced urinary calcium
excretion, this suggests that a high-protein, calcium-replete diet may protect
against bone loss during weight reduction.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14988448 [PubMed]
46: Am J Clin Nutr. 2004 Mar;79(3):352-61.
Effect of conjugated linoleic acid on body composition and plasma lipids in
humans: an overview of the literature.
Terpstra AH.
Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Utrecht
University, Utrecht, Netherlands. a.h.m.terpstra@las.vet.uu.nl
Studies in mice have indicated that feeding diets containing 0.5-1% conjugated
linoleic acid (CLA) considerably reduces body fat. These findings have attracted
much interest because of the potential use of CLA as a tool to promote weight
loss in humans. Several CLA studies in humans have now been published, and the
objective of the present review was to give an overview of these experiments.
Most of the studies were done in free-living subjects and were not strictly
controlled for nutrient and energy intakes. None of the studies found a
significant reduction in body weight, and only 2 studies showed a significant
but relatively small body fat-lowering effect. Some studies suggested that CLA
may have a tendency to increase lean body mass. Furthermore, there are
indications from animal studies that CLA may have effects on plasma lipids.
However, only one study in humans showed a significant HDL-cholesterol-lowering
effect of CLA; in all the other studies, there were no significant effects on
plasma total, LDL-, and HDL-cholesterol concentrations or on plasma
triacylglycerol concentrations. Thus, the results of the studies in humans
indicate that the effect of CLA on body fat is considerably less than that
anticipated from mice studies and that CLA has no major effect on plasma lipids.
Publication Types:
Review
Review, Tutorial
PMID: 14985207 [PubMed]
47: Biochim Biophys Acta. 2004 Feb 27;1636(1):59-68.
Induction of lipolysis in vitro and loss of body fat in vivo by
zinc-alpha2-glycoprotein.
Russell ST, Zimmerman TP, Domin BA, Tisdale MJ.
Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET,
UK.
Loss of adipose tissue in cancer cachexia has been associated with tumour
production of a lipid-mobilizing factor (LMF) which has been shown to be
homologous with the plasma protein zinc-alpha(2)-glycoprotein (ZAG). The aim of
this study was to compare the ability of human ZAG with LMF to stimulate
lipolysis in vitro and induce loss of body fat in vivo, and to determine the
mechanisms involved. ZAG was purified from human plasma using a combination of Q
Sepharose and Superdex 75 chromatography, and was shown to stimulate glycerol
release from isolated murine epididymal adipocytes in a dose-dependent manner.
The effect was enhanced by the cyclic AMP phosphodiesterase inhibitor Ro20-1724,
and attenuated by freeze/thawing and the specific beta3-adrenoreceptor
antagonist SR59230A. In vivo ZAG caused highly significant, time-dependent,
decreases in body weight without a reduction in food and water intake. Body
composition analysis showed that loss of body weight could be attributed
entirely to the loss of body fat. Loss of adipose tissue may have been due to
the lipolytic effect of ZAG coupled with an increase in energy expenditure,
since there was a dose-dependent increase in expression of uncoupling protein-1
(UCP-1) in brown adipose tissue. These results suggest that ZAG may be effective
in the treatment of obesity.
PMID: 14984739 [PubMed]
48: Nutr Metab Cardiovasc Dis. 2003 Dec;13(6):349-56.
Relationships between changes in abdominal fat distribution and insulin
sensitivity during a very low calorie diet in abdominally obese men and women.
Laaksonen DE, Kainulainen S, Rissanen A, Niskanen L.
Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
david.laaksonen@uku.fi
BACKGROUND AND AIM: Little is known about the association between abdominal
obesity and insulin sensitivity during rapid weight loss. We assessed the role
of visceral and subcutaneous fat as determinants of insulin sensitivity during
rapid weight loss in obese persons with the metabolic syndrome. METHODS AND
RESULTS: Twenty abdominally obese individuals [11 women and 9 men, body mass
index (BMI) 35.8+/-3.5 kg/m2] with the metabolic syndrome underwent a
very-low-calorie diet (VLCD) for nine weeks. At baseline, the computed
tomography (CT) measured area of total (r=-0.50, p=0.033) and visceral fat
tissue (r=-0.48, p=0.043), but not that of subcutaneous fat tissue (r=-0.34,
p=0.17), correlated with insulin sensitivity as assessed by the quantitative
insulin sensitivity check index after adjusting for sex and age. The 18 subjects
who completed the study lost 14.8 kg during the VLCD. Total, visceral and
subcutaneous abdominal fat tissue decreased by 22%, 29% and 17%, respectively.
The decrease in total (r=-0.51, p=0.035) and subcutaneous abdominal fat
(r=-0.57, p=0.017), but not visceral fat (r=0.11, p=0.68), correlated with the
increase in insulin sensitivity. Waist circumference did not offer any
additional information concerning abdominal fat distribution or insulin
sensitivity compared with that provided by BMI at baseline or after weight loss.
The waist/hip ratio was not associated with the CT measures of abdominal fat
distribution or insulin sensitivity. CONCLUSIONS: Total abdominal fat may be
more important than its compartmentalisation in abdominally obese individuals
with the metabolic syndrome. In this subgroup of individuals with obesity, the
measurement of waist circumference and the waist/hip ratio offered little
additional information over that provided by BMI at baseline or after weight
loss.
PMID: 14979681 [PubMed]
49: Endocrinology. 2004 Feb 19 [Epub ahead of print]
Fibroblast growth factor 19 increases metabolic rate and reverses dietary and
leptin deficient diabetes.
Fu L, John LM, Adams SH, Xian Yu X, Tomlinson E, Renz M, Mickey Williams P,
Soriano R, Corpuz R, Moffat B, Vandlen R, Simmons L, Foster J, Stephan JP, Ping
Tsai S, Stewart TA.
Departments of Molecular Biology, Protein Engineering and Assay Technologies,
Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080.
Hormonal control of metabolic rate can be important in regulating the imbalance
between energy intake and expenditure that underlies the development of obesity.
In mice fed a high fat diet, human fibroblast growth factor 19 (FGF19) increased
metabolic rate (1.53 +/- 0.06 L 02/hr/kg(0.75) (vehicle) vs. 1.93 +/- 0.05 L
02/hr/kg(0.75) (FGF19); P < 0.001) and decreased RQ (0.82 +/- 0.01 (vehicle) vs.
0.80 +/- 0.01 (FGF19); P < 0.05). In contrast to the vehicle treated mice that
gained weight (0.14 +/- 0.05 g/mouse/day), FGF19 treated mice lost weight (-0.13
+/- 0.03 g/mouse/day; P < 0.001) without a significant change in food intake.
Furthermore, in addition to a reduction in weight gain, treatment with FGF19
prevented or reversed the diabetes that develops in mice made obese by genetic
ablation of brown adipose tissue, or genetic absence of leptin. To explore the
mechanisms underlying the FGF19 mediated increase in metabolic rate, we profiled
the FGF19 induced gene expression changes in the liver and brown fat. In BAT,
chronic exposure to FGF19 led to a gene expression profile that is consistent
with activation of this tissue. We also found that FGF19 acutely increased liver
expression of the leptin receptor (1.8 fold; P < 0.05) and decreased the
expression of acetyl CoA carboxylase 2 (0.6 fold; P < 0.05). The gene expression
changes were consistent with the experimentally determined increase in fat
oxidation and decrease in liver triglycerides. Thus, FGF19 is able to increase
metabolic rate concurrently with an increase in fatty acid oxidation.
PMID: 14976145 [PubMed]
50: Ann Ital Med Int. 2003 Oct-Dec;18(4):238-45.
Body habitus changes, metabolic abnormalities, osteopenia and cardiovascular
risk in patients treated for human immunodeficiency virus infection.
Cirelli A, Cirelli G, Balsamo G, Masciangelo R, Stasolla A, Marini M.
S.S. Chemioantibioticoterapia Monitorizzata/AIDS, Dipartimento di Malattie
Infettive e Tropicali, Universita degli Studi "La Sapienza", Policlinico Umberto
I di Roma.
The aim of this study was to evaluate the influence of three variables--protease
inhibitors, stavudine, and the length of combined therapy--on body habitus
changes, metabolic effects and bone mineral density in HIV patients treated with
highly active antiretroviral therapy (HAART). The onset of possible
cardiovascular involvement was considered. Forty HIV patients (29 men and 11
women, mean age 39.13 +/- 7.82 years, range 28-61 years) treated with HAART for
12-43 months were evaluated for fat, lean, bone tissues, immunohematological and
cardiovascular alterations. The differences in fat/lean tissues and bone mineral
density were evaluated at dual-energy X-ray absorptiometry (DEXA). Serum lipids
and the CD4/CD8 T-cell counts were recorded. ECGs were taken every 6 months;
color Doppler echocardiography and color Doppler ultrasounds of the carotid
vessels were performed in close chronological sequence with the second DEXA.
Statistical analyses included: Student's t-test, Wilcoxon test, and
single-multiple regression analysis. Thirteen patients presented with fat loss,
7 fat accumulation, and 20 a combined form of both. The changes in the single
body districts showed that the decrease in the limb fat is to be attributed to
protease inhibitors, while none of the three variables was responsible for the
decrease in the upper limb fat. The trunk weight increase was not significant.
The decrease in the lean mass of the upper limbs is to be attributed to protease
inhibitors, while none of the three variables was responsible for the increase
in the lean mass of the upper and lower limbs. The decrease in bone mineral
density was not significant. No treatment-related cardiovascular lesions were
observed. In HIV patients treated with HAART for 12-43 months, the decrease in
lower limb fat was due to protease inhibitors. Neither osteopenia nor
cardiovascular diseases were observed during follow-up.
PMID: 14971712 [PubMed]
51: J Sports Sci. 2004 Jan;22(1):31-8.
Pre-exercise carbohydrate and fat ingestion: effects on metabolism and
performance.
Hargreaves M, Hawley JA, Jeukendrup A.
Centre for Physical Activity and Nutrition Research, School of Health Sciences,
Deakin University, Burwood, Vic 3125, Australia. mharg@deakin.edu.au
A key goal of pre-exercise nutritional strategies is to maximize carbohydrate
stores, thereby minimizing the ergolytic effects of carbohydrate depletion.
Increased dietary carbohydrate intake in the days before competition increases
muscle glycogen levels and enhances exercise performance in endurance events
lasting 90 min or more. Ingestion of carbohydrate 3-4 h before exercise
increases liver and muscle glycogen and enhances subsequent endurance exercise
performance. The effects of carbohydrate ingestion on blood glucose and free
fatty acid concentrations and carbohydrate oxidation during exercise persist for
at least 6 h. Although an increase in plasma insulin following carbohydrate
ingestion in the hour before exercise inhibits lipolysis and liver glucose
output, and can lead to transient hypoglycaemia during subsequent exercise in
susceptible individuals, there is no convincing evidence that this is always
associated with impaired exercise performance. However, individual experience
should inform individual practice. Interventions to increase fat availability
before exercise have been shown to reduce carbohydrate utilization during
exercise, but do not appear to have ergogenic benefits.
PMID: 14971431 [PubMed]
52: J Inherit Metab Dis. 2004;27(1):89-99.
The distribution of white blood cell fat oxidation in health and disease.
Pendergast DR, Fisher NM, Meksawan K, Doubrava M, Vladutiu GD.
Department of Physiology, University at Buffalo, Buffalo, New York 14214, USA.
dpenderg@buffalo.edu
Fat oxidation is important for maintaining health and for supplying energy for
exercise. We have proposed that the predisposition for individual rates of fat
oxidation is determined genetically but may be modulated by acute exercise or
exercise training. The purpose of this study was to examine cellular fat
oxidation in white blood cells (WBC) using [9,10-3H]palmitic acid. Sedentary
controls free of symptoms (SED-C, n=32), were compared with known carnitine
palmitoyltransferase (CPT) II-deficient patients (n =2), patients with fatiguing
diseases (chronic fatigue syndrome, CFS, n=6; multiple sclerosis, MS, n=31),
obesity (OB, n=5), eating disorders (ED, n=16), sedentary individuals prior to
and after exercise (SED-Ex, n=12), exercise-trained sedentary individuals
(SED-Tr, n=12), and elite runners (ER, n=5). Fat oxidation in WBC for all
subjects was normally distributed (mean=0.270 +/- 0.090 nmol/h per 10(9) WBC)
and ranged from 0.09 nmol/h per 10(9) WBC in CPT II-deficient patients to 0.59
nmol/h per 10(9) WBC in ER. There were no significant sex or acute exercise
effects on WBC fat oxidation. Patients with MS, OB or ED were not different from
SED-C; however, in CPT II-deficient patients, fat oxidation was low, while that
of CFS patients was high. Exercise training in SED-C resulted in a 16% increase
in fat oxidation but in ER it was still 97% higher than in SED-C. We propose
that while WBC fat oxidation is not significantly affected by sex or acute
exercise, and only by 15-20% with training, genetic factors play a role in
determining both high and low fat oxidation in certain groups of individuals.
The genetic predisposition for individual rates of fat oxidation may be easily
measured using WBC fat oxidation, as has been shown for CPT II-deficient
patients and for elite runners. Ranges of WBC fat oxidation that are abnormally
low (<20 nmol/h per 10(9) WBC, normal 20-35) or high (>35 nmol/h per 10(9) WBC)
are proposed based on genetic factors evaluated in this study.
PMID: 14970749 [PubMed]
53: J Appl Physiol. 2004 Feb 13 [Epub ahead of print]
Pyruvate dehydrogenase activation and kinase expression inhuman skeletal muscle
during fasting.
Spriet LL, Tunstall RJ, Watt MJ, Mehan KA, Hargreaves M, Cameron-Smith D.
Department of Human Biology and Nutritional Sciences, University of Guelph,
Guelph, Ontario, Canada.
Fasting forces adaptive changes in whole body and skeletal muscle metabolism
that increase fat oxidation and decrease the oxidation of carbohydrate. We
tested the hypothesis that 40 h of fasting would decrease pyruvate dehydrogenase
(PDH) activity and increase PDH kinase isoform (PDK1-4) mRNA expression in human
skeletal muscle. The putative transcriptional activators of PDK isozymes,
peroxisome proliferator-activated receptor alpha (PPARalpha) protein and
forkhead homolog in rhabdomyosarcoma (FKHR) mRNA were also measured. Eleven
healthy adults fasted following a standard meal (25% fat, 60% carbohydrate, 15%
protein) with blood and skeletal muscle samples taken at 3, 15, and 40 h post
prandial. Fasting increased plasma free fatty acid, glycerol and
beta-hydroxybutyrate concentrations and decreased glucose and insulin
concentrations. PDH activation decreased from 0.88 +/- 0.11 mmol
acetyl-CoA/min/kg wet muscle at 3 h to 0.62 +/- 0.10 (NS) and 0.39 +/- 0.06
(p<0.05) mmol/min/kg wet mass following 15 and 40 h of fasting. While all four
PDK isoforms were expressed in human skeletal muscle, PDK2 and 4 mRNA were the
most abundant. PDK1 and 3 mRNA abundance was ~ 1% and 15% of the PDK2 and PDK4
levels, respectively. The 40 h fast had no effect on PDK1, 2 and 3 mRNA
expression. PDK4 mRNA was significantly increased ~3-fold after 15 h and
~14-fold after 40 h of fasting. Skeletal muscle PPARalpha protein and FKHR mRNA
abundance were unaffected by the fast. The results suggest that decreased PDH
activation following 40 h of fasting may have been a function of the large
increase in PDK4 mRNA expression and possible subsequent increase in PDK protein
and activity. The changes in PDK4 expression and PDH activity did not coincide
with increases in the transcriptional activators, PPARalpha and FKHR.
PMID: 14966024 [PubMed]
54: J Endocrinol Invest. 2003 Sep;26(9):902-10.
Effects of estrogen replacement on metabolic factors that influence physical
performance in female hypogonadism.
Kohrt WM, Van Pelt RE, Gozansky WS.
Division of Geriatric Medicine, Department of Medicine, University of Colorado
Health Sciences Center, Denver, Colorado 80262, USA. wendy.kohrt@uchsc.edu
There is a lack of knowledge regarding the effects of estrogens on physical
performance. This is related, in part, to the challenge of isolating the effects
of estrogens from those of progestins, because levels of both hormones fluctuate
across the menstrual cycle, both decline during the menopausal transition, and
the administration oh hormones to hypogonadal women typically involves a
combination of estrogens and progestins. Some research findings suggest that
fluctuations in estrogen levels acutely influence factors that may affect
physical performance, such as substrate utilization or maximal aerobic power,
but solid evidence is lacking. The simple observation that hypogonadism is not
uncommon among elite athletes in some sports suggests that estrogen deficiency
does not have a major negative impact on athletic performance. However, chronic
hypogonadism may ultimately lead to impaired performance by menas that are not
necessarily obvious. For example, chronic estrogen deficiency has potent,
deleterious effects on the skeleton that can increase risk for stress fracture
and may limit the ability to sustain a high level of physical training. Estrogen
deficiency also appears to promote fat accumulation and may accelerate the loss
of fat-free mass, and both of these changes in body composition could impair
physical performance. There is evidence that hormone replacement attenuates the
negative effects of hypogonadism on body composition and bone density, and that
effects are mediated primarily by estrogens rather than progestins. Further
research is necessary to broaden the understanding of the role of the estrogens
in physical performance.
PMID: 14964444 [PubMed]
55: J Endocrinol Invest. 2003 Sep;26(9):893-901.
Body composition and muscle performance during menopause and hormone replacement
therapy.
Sipila S.
Department of Health Sciences, University of Jyvaskyla, Finland.
sipila@sport.jyu.fi
Menopausal transition is characterized by ovarian failure and its consequent
decrease in female sex steroid production. Earlier studies suggest that an
increase and redistribution of body fat during menopause predispose women to
cardiovascular disease and metabolic syndrome. In addition, peri- and
post-menopausal women seem to have less lean body mass (LBM) compared with
pre-menopausal women. Accordingly, a changing ovarian hormonal status may
accelerate the loss of muscle mass and result in decreased muscle performance
and functional capacity. Hormone replacement therapy (HRT) has been used to
treat menopausal symptoms and as a primary prevention therapy in chronic
conditions. Inconsistent findings have, however, been published on the effects
of HRT on body composition in post-menopausal women. Some studies clearly
suggest that HRT counteracts menopause-related changes in body composition
whereas others fail to show any difference between post-menopausal HRT users and
abstainers. Although cross-sectional studies show conflicting results concerning
the association between HRT and muscle performance, experimental trials suggest
that deterioration in muscle force during menopause can be prevented by HRT. In
the future, longitudinal data need to be collected to confirm changes in body
composition and muscle performance during menopausal transition irrespective of
age. Although HRT seems to have beneficial effects on body composition and
muscle performance in healthy post-menopausal women, there is considerable
variation in the effects of HRT between different studies. The underlying
mechanism of HRT action on muscle performance is still unclear.
PMID: 14964443 [PubMed]
56: Adv Ther. 2003 Sep-Oct;20(5):270-81.
Master Amino acid Pattern as sole and total substitute for dietary proteins
during a weight-loss diet to achieve the body's nitrogen balance equilibrium.
Luca-Moretti M, Grandi A, Luca E, Muratori G, Nofroni MG, Mucci MP, Gambetta P,
Stimolo R, Drago P, Giudice G, Tamburlin N, Karbalai M, Valente C, Moras G.
American Nutrition Clinics, Coral Gables, FL 33143, USA.
Results of this multicentric study have shown that by giving Master Amino acid
Pattern (MAP) as a sole and total substitute of dietary proteins to 500
overweight participants undergoing the American Nutrition Clinics/Overweight
Management Program (ANC/OMP), the participants' body nitrogen balance could be
maintained in equilibrium with essentially no calories (MAP 1 g=0.04 kcal),
thereby preserving the body's structural and functional proteins, eliminating
excessive water retention from the interstitial compartment, and preventing the
sudden weight increase after study conclusion commonly known as the yo-yo
effect. Study results have shown that the use of MAP, in conjunction with the
ANC/OMP regimen, has proven to be safe and effective by preventing those adverse
effects associated with a negative nitrogen balance, such as oversized or flabby
tissue, stretch marks, the sagging of breast tissue, increased hair loss, faded
hair color, and fragile or brittle nails. Also prevented were those anomalies
commonly associated with weight-loss diets, such as hunger, weakness, headache
caused by ketosis, constipation, and decreased libido. The use of MAP in
conjunction with the ANC/OMP also allowed for mean weight loss of 2.5 kg (5.5
lb) per week, achieved through reduction of excessive fat tissue and elimination
of excessive water retention from the interstitial compartment.
Publication Types:
Clinical Trial
Multicenter Study
PMID: 14964347 [PubMed]
57: Dev Cell. 2004 Feb;6(2):241-51.
Comment in:
Dev Cell. 2004 Feb;6(2):163-4.
Drosophila cyclin D/Cdk4 requires Hif-1 prolyl hydroxylase to drive cell growth.
Frei C, Edgar BA.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, P.O. Box
19024, Seattle, WA 98109, USA. christian.frei@zool.unizh.ch
The Drosophila cyclin-dependent protein kinase complex Cyclin D/Cdk4 induces
cell growth (accumulation of mass) as well as proliferation (cell cycle
progression). To understand how CycD/Cdk4 promotes growth, we performed a screen
for modifiers of CycD/Cdk4-driven overgrowth in the eye. Loss-of-function
mutations in Hif-1 prolyl hydroxylase (Hph), an enzyme involved in the cellular
response to hypoxic stress, dominantly suppress the growth but not the
proliferation function of CycD/Cdk4. hph mutant cells are defective for growth,
and, remarkably, ectopic expression of Hph is sufficient to increase cellular
growth. Epistasis analysis places Hph downstream of CycD/Cdk4. Overexpressed
CycD/Cdk4 causes an increase in Hph protein in tissues where Hph induces growth,
suggesting a mechanism whereby Hph levels are regulated posttranscriptionally in
response to CycD/Cdk4. Our data suggest that Hph, in addition to its function in
hypoxic response, is a regulator of cellular growth and that it is a key
mediator for CycD/Cdk4.
PMID: 14960278 [PubMed]
58: Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2058-63. Epub 2004 Feb 09.
Rapid transformation of white adipocytes into fat-oxidizing machines.
Orci L, Cook WS, Ravazzola M, Wang MY, Park BH, Montesano R, Unger RH.
Department of Morphology, University of Geneva Medical School, Rue Michel Servet
1, CH 1211 Geneva 4, Switzerland. lelio.orci@medecine.unige.ch
Adenovirus-induced hyperleptinemia rapidly depletes body fat in normal rats
without increasing free fatty acids and ketogenesis, implying that fat-storing
adipocytes are oxidizing the fat. To analyze the ultrastructural changes of
adipocytes accompanying this functional transformation, we examined the fat
tissue by electron microscopy. After 14 days of hyperleptinemia, adipocytes had
become shrunken, fatless, and encased in a thick basement-membrane-like matrix.
They were crowded with mitochondria that were much smaller than those of brown
adipocytes. Their gene expression profile revealed striking up-regulation of
peroxisome proliferator-activated receptor gamma coactivator 1alpha (an
up-regulator of mitochondrial biogenesis not normally expressed in white fat),
increased uncoupling proteins-1 and -2, and down-regulation of lipogenic
enzymes. Phosphorylation of both acetyl CoA carboxylase and AMP-activated
protein kinase was increased, thus explaining the increase in fatty acid
oxidation. The ability to transform adipocytes into unique fat-burning cells may
suggest novel therapeutic strategies for obesity.
PMID: 14769942 [PubMed]
59: Maturitas. 2004 Feb 20;47(2):99-105.
Relationship between soft tissue body composition and bone mass in
perimenopausal women.
Li S, Wagner R, Holm K, Lehotsky J, Zinaman MJ.
Loyola University, Chicago, IL 60153, USA. sli@luc.edu
OBJECTIVES: Perimenopause, the transition into menopause, marks the beginning of
accelerated bone loss, contributing to the development of osteoporosis, a major
public health problem. This perimenopausal transition has also been associated
with a decrease in body lean mass, an increase in fat mass, and an increase in
body weight. How these changes in fat mass and lean mass may influence bone
mineral density (BMD) is currently unknown. The purpose of this study is to
determine the independent effect and relative contribution of lean mass and fat
mass to BMD in perimenopausal women. MATERIAL AND METHODS: The sample consisted
of 43 sedentary perimenopausal women (age: mean = 49.6; S.D. = 3.2) with an
intact uterus and ovaries, participating in a study of exercise and
perimenopausal symptoms. Total body BMD, regional BMD, and soft tissue body
composition were measured by dual-energy X-ray absorptiometry. Other measures
including age, height, weight, and serum FSH and E2 were also obtained. RESULTS:
Findings revealed that 14% of these perimenopausal women had low bone mass
(osteopenia) in the lumbar spine and/or the femoral neck. Overall body fat mass
and lean mass had positive relationships with BMD of lumber spine and the femur.
However, using multiple regression analyses, only lean mass and ethnicity
remained significant predictors for BMD of the femoral neck (r2 = 45%) with lean
mass explaining more variance than ethnicity. Lean mass was the sole predictor
of total proximal femur BMD explaining 38% of the variance. Fat mass was not a
significant predictor of BMD at any skeleton site. CONCLUSIONS: These findings
suggest that body lean mass, not fat mass, is a significant contributor to
femoral BMD in perimenopausal women.
PMID: 14757268 [PubMed]
60: Br J Nutr. 2004 Feb;91(2):245-52.
The acute effects of olive oil v. cream on postprandial thermogenesis and
substrate oxidation in postmenopausal women.
Soares MJ, Cummings SJ, Mamo JC, Kenrick M, Piers LS.
Department of Nutrition, Dietetics and Food Science, School of Public Health,
Curtin University of Technology, GPO Box U 1987, Perth WA 6845, Australia.
m.soares@curtin.edu.au
The influence of the source of dietary fat on postprandial thermogenesis and
substrate oxidation rates, was examined in twelve postmenopausal women aged
57-73 years, with BMI 21.9-38.3 kg/m(2). A single blind, randomised, paired
comparison of two high-fat, isoenergetic, mixed test meals was conducted. The
major source of fat was either cream (CREAM) or extra virgin olive oil (EVOO).
RMR, diet-induced thermogenesis (DIT) and substrate oxidation rates over 5 h
were measured by indirect calorimetry. There were no differences in body weight,
RMR, fasting carbohydrate or fat oxidation rates between the two occasions. DIT
(EVOO 97 (SD 46) v. CREAM 76 (SD 69) kJ/5 h and EVOO 5.2 (SD 2.5) v. CREAM 4.1
(SD 3.7)% energy) did not differ between the two test meals. The postprandial
increase in carbohydrate oxidation rates, relative to their respective fasting
values (DeltaCOX), was significantly lower following the EVOO meal (EVOO 10.6
(SD 8.3) v. CREAM 17.5 (SD 10) g/5 h; paired t test, P=0.023), while
postprandial fat oxidation rates (DeltaFOX) were significantly higher (EVOO 0.0
(SD 4.4) v. CREAM -3.6 (sd 4.0) g/5 h; P=0.028). In the eight obese subjects,
however, DIT was significantly higher following the EVOO meal (EVOO 5.1 (SD 2.0)
v. CREAM 2.5 (sd 2.9) %; P=0.01). This was accompanied by a significantly lower
DeltaCOX (EVOO 10.9 (SD 9.9) v. CREAM 17.3 (SD 10.5) g/5 h; P=0.03) and
significantly higher DeltaFOX (EVOO 0.11 (SD 4.4) v. CREAM -4.1 (SD 4.5) g/5 h,
P=0.034). The present study showed that olive oil significantly promoted
postprandial fat oxidation and stimulated DIT in abdominally obese
postmenopausal women.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14756910 [PubMed]
61: J Agric Food Chem. 2004 Feb 11;52(3):587-91.
Effect of antioxidants on oxidative stability of edible fats and oils:
thermogravimetric analysis.
van Aardt M, Duncan SE, Long TE, O'Keefe SF, Marcy JE, Sims SR.
Department of Food Science and Technology, Virginia Polytechnic Institute and
State University, Duck Pond Drive, Blacksburg, Virginia 24061, USA.
mvanaard@vt.edu
Thermogravimetric analysis was used to determine the oxidative stability of
various edible oils (olive oil, milkfat) and triacylglycerides (triolein,
trilinolein), while the effect of natural (alpha-tocopherol, ascorbic acid) and
synthetic antioxidants (butylated hydroxytoluene (BHT), butylated hydroxyanisole
(BHA), and tertiary butyl hydroquinone were evaluated by addition to
trilinolein. Oil resistance to oxidation was obtained by measuring the increase
in sample weight due to the uptake of molecular oxygen, the temperature at
maximum sample weight, and the temperature at the onset of oxidation. When
comparing sample weight increase, trilinolein proved to be oxidatively less
stable than triolein, olive oil, and milk fat, while triolein was less stable
than olive oil and milk fat. Olive oil showed significantly higher stability
than milkfat when comparing the temperature at the onset of oxidation. When
comparing effectiveness of antioxidants, a combination of 0.01% BHA and 0.01%
BHT increased trilinolein stability the most.
PMID: 14759153 [PubMed]
62: Int J Sports Med. 2004 Jan;25(1):32-7.
Relation between plasma lactate concentration and fat oxidation rates over a
wide range of exercise intensities.
Achten J, Jeukendrup AE.
School of Sport and Exercise Sciences, University of Birmingham, Edgbaston,
Birmingham B15 2TT, United Kingdom.
Increasing exercise intensities will induce an increase in glycolytic flux. High
glycolytic activity is associated with reduced fat oxidation rates and increased
accumulation of lactate. Both lactate and hydrogen ions have been shown to be
directly related to the decreased fat oxidation rates. The aim of the present
study was to determine whether the exercise intensity at which maximal fat
oxidation rates occur coincides with the intensity at which lactate starts to
accumulate in plasma. Thirty-three moderately trained endurance athletes
performed a graded exercise test to exhaustion on a cycle-ergometer with 35 W
increments every three minutes. Expired gas analysis was performed throughout
the test and stoichiometric equations were used to calculate fat oxidation
rates. The intensity which elicited maximal fat oxidation (Fat (max)) and the
intensity at which fat oxidation rates became negligible (Fat (min)) were
determined. Blood samples for lactate analysis were collected at the end of each
stage of the graded exercise test. The intensity at which lactate concentration
increased above baseline (LIAB) and the lactate threshold (LT-D) were determined
(D-max method). Fat (max) was located at 63 +/- 9 % V.O (2)max and LIAB at 61
+/- 5 % V.O (2)max and there appeared to be no statistical difference between
the two intensities. Fat (max) and LIAB were significantly correlated. Fat (min)
and LT-D were also significantly correlated but were located at different
intensities (82 +/- 7 and 87 +/- 9 % V.O (2)max respectively). The data of the
present study showed that accumulation of lactate in plasma is strongly
correlated to the reduction seen in fatty acid oxidation with increasing
exercise intensities. The first rise of lactate concentration occurred at the
same intensity as the intensity which elicited maximal fat oxidation rates.
PMID: 14750010 [PubMed]
63: Eur J Clin Nutr. 2004 Feb;58(2):244-9.
Effects of elderberry juice on fasting and postprandial serum lipids and
low-density lipoprotein oxidation in healthy volunteers: a randomized,
double-blind, placebo-controlled study.
Murkovic M, Abuja PM, Bergmann AR, Zirngast A, Adam U, Winklhofer-Roob BM,
Toplak H.
Department of Food Chemistry and Technology, Graz University of Technology,
Graz, Austria. michael.murkovic@tugraz.at
BACKGROUND: In a recent pilot study, the intake of elderberry juice resulted in
a significant decrease in serum cholesterol concentrations and an increase in
low-density lipoprotein (LDL) stability. This study was designed to verify the
preliminary results. OBJECTIVE: We investigated the impact of elderberry juice
on cholesterol and triglyceride concentrations as well as antioxidant status in
a cohort of young volunteers. DESIGN: Study A: The randomized,
placebo-controlled trial for studying the effect of anthocyanes on lipid and
antioxidant status, 34 subjects took capsules with 400 mg spray-dried powder
containing 10% anthocyanes t.i.d. equivalent to 5 ml elderberry juice for 2
weeks. A subgroup of 14 subjects continued for an additional week to test for
resistance to oxidation of LDL. Study B: To investigate the short-term effects
on serum lipid concentrations, six subjects took a single dose of 50 ml of
elderberry juice (equivalent to 10 capsules) along with a high-fat breakfast.
RESULTS: In the placebo-controlled study, there was only a small, statistically
not significant change in cholesterol concentrations in the elderberry group
(from 199 to 190 mg/dl) compared to the placebo group (from 192 to 196 mg/dl).
The resistance to copper-induced oxidation of LDL did not change within 3 weeks.
In the single-dose experiment increases in postprandial triglyceride
concentrations were not significantly different when the six subjects were
investigated with and without elderberry juice. CONCLUSIONS: Elderberry
spray-dried extract at a low dose exerts a minor effect on serum lipids and
antioxidative capacity. Higher, but nutritionally relevant doses might
significantly reduce postprandial serum lipids.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14749743 [PubMed]
64: Recent Prog Horm Res. 2004;59:225-44.
Leptin and the cardiovascular system.
Rahmouni K, Haynes WG.
Department of Internal Medicine, and General Clinical Research Center,
University of Iowa, Iowa City, Iowa 52242, USA.
Obesity is associated with increased cardiovascular morbidity and mortality, in
part through development of hypertension. Recent observations suggest that the
cardiovascular actions of leptin may help explain the link between excess fat
mass and cardiovascular diseases. Leptin is an adipocyte-derived hormone that
acts in the central nervous system to promote weight loss by decreasing food
intake and increasing metabolic rate. Leptin causes a significant increase in
overall sympathetic nervous activity, which appears to be due to direct
hypothalamic effects and is mediated by neuropeptide systems such as the
melanocortin system and corticotropin-releasing hormone. Renal
sympathoactivation to leptin is preserved in the presence of obesity, despite
resistance to the metabolic effects of leptin. Such selective leptin resistance,
in the context of circulating hyperleptinemia, could predispose to
obesity-related hypertension. Some in vitro studies have suggested that leptin
may have peripheral actions such as endothelium-mediated vasodilation that might
oppose sympathetically induced vasoconstriction. However, we and others have
shown that leptin does not have direct vasodilator effects in vivo. The fact
that chronic leptin administration or overexpression of leptin produces
hypertension supports the concept that the hemodynamic actions of leptin are due
predominantly to sympathetic activation. Exploration of the sites and mechanisms
of leptin resistance should provide novel therapeutic strategies for obesity,
insulin resistance, and hypertension.
Publication Types:
Review
Review, Tutorial
PMID: 14749504 [PubMed]
65: Diabetes. 2004 Feb;53 Suppl 1:S143-51.
Update on adipocyte hormones: regulation of energy balance and
carbohydrate/lipid metabolism.
Havel PJ.
Department of Nutrition, University of California, Davis, Davis, California
95616, USA. pjhavel@ucdavis.edu
Hormones produced by adipose tissue play a critical role in the regulation of
energy intake, energy expenditure, and lipid and carbohydrate metabolism. This
review will address the biology, actions, and regulation of three adipocyte
hormones-leptin, acylation stimulating protein (ASP), and adiponectin-with an
emphasis on the most recent literature. The main biological role of leptin
appears to be adaptation to reduced energy availability rather than prevention
of obesity. In addition to the well-known consequences of absolute leptin
deficiency, subjects with heterozygous leptin gene mutations have low
circulating leptin levels and increased body adiposity. Leptin treatment
dramatically improves metabolic abnormalities (insulin resistance and
hyperlipidemia) in patients with relative leptin deficiency due to lipoatrophy.
Leptin production is primarily regulated by insulin-induced changes of adipocyte
metabolism. Dietary fat and fructose, which do not increase insulin secretion,
lead to reduced leptin production, suggesting a mechanism for
high-fat/high-sugar diets to increase energy intake and weight gain. ASP
increases the efficiency of triacylglycerol synthesis in adipocytes leading to
enhanced postprandial lipid clearance. In mice, ASP deficiency results in
reduced body fat, obesity resistance, and improved insulin sensitivity.
Adiponectin production is stimulated by thiazolidinedione agonists of peroxisome
proliferator-activated receptor-gamma and may contribute to increased insulin
sensitivity. Adiponectin and leptin cotreatment normalizes insulin action in
lipoatrophic insulin-resistant animals. These effects may be mediated by AMP
kinase-induced fat oxidation, leading to reduced intramyocellular and liver
triglyceride content. The production of all three hormones is influenced by
nutritional status. These hormones, the pathways controlling their production,
and their receptors are promising targets for managing obesity, hyperlipidemia,
and insulin resistance.
Publication Types:
Review
Review, Academic
PMID: 14749280 [PubMed]
66: Am J Physiol Endocrinol Metab. 2004 Jan 28 [Epub ahead of print]
Reduced plasma FFA availability increases net triacylglycerol degradation, but
not GPAT or HSL activity in human skeletal muscle.
Watt MJ, Holmes AG, Steinberg GR, Mesa JL, Kemp BE, Febbraio MA.
Skeletal Muscle Research Laboratory, Royal Melbourne Institute of Technology,
Bundoora, Victoria, Australia.
Intramuscular triacylglycerols (IMTG) are proposed to be an important metabolic
substrate for contracting muscle, although this remains controversial. To test
the hypothesis that reduced plasma FFA availability would increase IMTG
degradation during exercise, seven active men cycled for 180 min at 60% VO2 peak
either without (CON) or with (NA) prior ingestion of nicotinic acid to suppress
adipose tissue lipolysis. Skeletal muscle and adipose tissue biopsy samples were
obtained before and at 90 and 180 min of exercise. NA ingestion decreased
(P<0.05) plasma FFA at rest and completely suppressed the exercise induced
increase in plasma FFA (180 min: CON, 1.42 +/- 0.07; NA, 0.10 +/- 0.01 mM). The
decreased plasma FFA during NA was associated with decreased (P<0.05) adipose
tissue hormone sensitive lipase (HSL) activity (CON: 13.9 +/- 2.5, NA: 9.1 +/-
3.0 nmol.min(-1).mg(-1) protein). NA ingestion resulted in decreased whole body
fat oxidation and increased carbohydrate oxidation. Despite the decreased whole
body fat oxidation, net IMTG degradation was greater in NA compared with CON
(net change: CON, 2.3 +/- 0.8; NA, 6.3 +/- 1.2 mmol.kg(-1) dm). The increased
IMTG degradation did not appear to be due to reduced fatty acid esterification
as glycerol-3-phosphate activity was not different between trials and was
unaffected by exercise (rest: 0.21 +/- 0.07; 180 min: 0.17 +/- 0.04
nmol.min.(-1)mg protein(-1)). HSL activity was not increased from resting rates
during exercise in either trial despite elevated plasma adrenaline, decreased
plasma insulin and increased ERK1/2 phosphorylation. AMPKalpha-1 activity was
not affected by exercise or NA, whereas AMPKalpha-2 activity was increased
(P<0.05) from rest during exercise in NA and was greater (P<0.05) than CON at
180 min. These data suggest that plasma FFA availability is an important
mediator of net IMTG degradation, and in the absence of plasma FFA, IMTG
degradation cannot maintain total fat oxidation. These changes in IMTG
degradation appear to disassociate, however, from the activity of the key
enzymes responsible for synthesis and degradation of this substrate.
PMID: 14749208 [PubMed]
67: Br J Nutr. 2004 Jan;91(1):153-9.
Effect of equilibrated hydration changes on total body water estimates by
bioelectrical impedance analysis.
Pialoux V, Mischler I, Mounier R, Gachon P, Ritz P, Coudert J, Fellmann N.
Laboratoire de Physiologie-Biologie du Sport, Faculte de Medecine, Universite
d'Auvergne, 28 place Henri Dunant, Clermont-Ferrand 63000, France.
The present study was performed to determine how equilibrated fluctuations in
hydration affected the validity of bioelectrical impedance analysis (BIA) for
body composition assessment. Total body water (TBW) expansion was induced by a 4
d endurance trial and the subsequent water loss was obtained over the recovery
period. Twelve healthy men exercised on a cycle and treadmill alternately for 5
h/d over 4 d at moderate intensity. TBW, fat mass (FM) and fat-free mass (FFM)
were assessed 3 d before the trial (control), and on the first and eighth day of
recovery (R1 and R8 respectively). TBW was evaluated by (2)H dilution (TBW2H) as
a reference method and by BIA (TBWBIA) at 100 kHz at the same time. TBW2H
increased significantly between the control day and R1 by 1.87 (sd 1.11) litres
(P=0.005) and TBWBIA by 1.38 (sd 1.56) litres (P=0.009). Both values returned to
the control level on R8. For each period, TBW2H and TBWBIA did not differ
significantly and were correlated (r(2) 0.85, P=0.0004 for the control day; r(2)
0.63, P=0.03 for R1; r(2) 0.75, P=0.02 for R8). Plasma Na concentration and
osmolality did not differ between the control day, R1 and R8. FFM gain (1208 (sd
1983) g) and FM loss (-1168 (sd 906) g) between the control day and R1 were
followed by a FFM decrease (-624 (sd 1281) g) and a FM increase (860 (sd 1212)
g) between R1 and R8. As expected, these FFM and FM changes were significantly
correlated with TBW variations. The present results provide evidence that BIA
may be a useful method for estimating TBW when fluid shifts are equilibrated and
electrolyte concentrations are unchanged. However, it is not a valid technique
for assessing FM and FFM under these conditions.
PMID: 14748949 [PubMed]
68: J Gastrointest Surg. 2004 Jan;8(1):48-55; discussion 54-5.
Serum fat-soluble vitamin deficiency and abnormal calcium metabolism after
malabsorptive bariatric surgery.
Slater GH, Ren CJ, Siegel N, Williams T, Barr D, Wolfe B, Dolan K, Fielding GA.
Wesley Hospital, Brisbane, Queensland, Australia. guyslater@msn.com
Weight loss after biliopancreatic diversion or duodenal switch is due to
decreased calorie absorption secondary to fat malabsorption. Fat malabsorption
may also cause essential fat-soluble vitamin deficiencies, which may have severe
clinical consequences and alter calcium metabolism. Serum vitamins A, D, E, and
K, zinc, parathyroid hormone, corrected calcium, and alkaline phosphatase levels
were measured in a cohort of patients who had previously undergone
biliopancreatic diversion. Two bariatric surgery units were involved in the
study: New York University School of Medicine (New York, NY), and the Wesley
Medical Center (Brisbane, Australia). A total of 170 patients completed the
study. The incidence of vitamin A deficiency was 69%, vitamin K deficiency 68%,
and vitamin D deficiency 63% by the fourth year after surgery. The incidence of
vitamin E and zinc deficiency did not increase with time after surgery. The
incidence of hypocalcemia increased from 15% to 48% over the study period with a
corresponding increase in serum parathyroid hormone values in 69% of patients in
the fourth postoperative year. There is a progressive increase in the incidence
and severity of hypovitaminemia A, D, and K with time after biliopancreatic
diversion and duodenal switch. Calcium metabolism is affected with an increasing
incidence of secondary hyperparathyrodisim and evidence of increased bone
resorption in 3% of patients. Long-term nutritional monitoring is necessary
after malabsorptive operations for morbid obesity.
PMID: 14746835 [PubMed]
69: Obes Res. 2004 Jan;12(1):32-9.
Regulation of lipolysis and lipoprotein lipase after weight loss in obese,
postmenopausal women.
Berman DM, Nicklas BJ, Ryan AS, Rogus EM, Dennis KE, Goldberg AP.
Division of Gerontology, Department of Medicine, University of Maryland School
of Medicine, Baltimore, Maryland, USA. Dberman2@med.miami.edu
OBJECTIVE: To test the hypothesis that the greater beta-adrenoceptor
(beta-AR)-stimulated lipolysis and sensitivity (half-maximal lipolytic response)
in abdominal (ABD) adipocytes, greater gluteal (GLT) adipose tissue-lipoprotein
lipase (AT-LPL) activity, and dyslipidemia associated with obesity in older
women are modifiable by weight loss (WL) and are not due to menopause or aging.
RESEARCH METHODS AND PROCEDURES: The metabolic effects of 6 months of
hypocaloric diet and low-intensity walking WL program on the regional regulation
of in vitro lipolysis and AT-LPL activity in subcutaneous ABD and GLT adipocytes
were measured in 34 obese (48.7 +/- 0.7% body fat, mean +/- SE) postmenopausal
(59 +/- 1 years) white women. RESULTS: The lipolytic responsiveness to the
beta-AR agonist isoproterenol and basal lipolysis in the presence of 1 U/mL
adenosine deaminase-uninhibited (lipolysis) were greater (p < 0.01) in ABD than
GLT adipocytes before and after WL, but there were no regional differences in
postreceptor (dibutyryl 3',5'-cyclic adenosine monophosphate)-stimulated
lipolysis. beta-AR sensitivity was greater in ABD than GLT adipocytes before (p
< 0.01) but not after WL. Regional AT-LPL did not change after WL, but the
change in the activity of ABD (but not GLT) AT-LPL correlated with the baseline
adenosine deaminase-uninhibited lipolysis (r = 0.38, p = 0.03). There were no
relationships between the declines in plasma triglyceride or increases in
high-density lipoprotein cholesterol associated with WL and the changes in
regional fat cell metabolism. DISCUSSION: Thus, despite improving lipoprotein
lipid profiles in obese, postmenopausal women, WL does not affect the regulation
of regional fat metabolism, and a greater tonic inhibition of basal lipolysis by
endogenous adenosine may increase the activity of AT-LPL after WL and predispose
older women to develop ABD adiposity.
PMID: 14742840 [PubMed]
70: Brain. 2004 Mar;127(Pt 3):692-700. Epub 2004 Jan 21.
Serial magnetization transfer imaging in acute optic neuritis.
Hickman SJ, Toosy AT, Jones SJ, Altmann DR, Miszkiel KA, MacManus DG, Barker GJ,
Plant GT, Thompson AJ, Miller DH.
NMR Research Unit, Department of Neuroinflammation, Institute of Neurology,
University College London, Queen Square, London WC1N 3BG, UK.
In serial studies of multiple sclerosis lesions, reductions in magnetization
transfer ratio (MTR) are thought to be due to demyelination and axonal loss,
with later rises due to remyelination. This study followed serial changes in MTR
in acute optic neuritis in combination with clinical and electrophysiological
measurements to determine if the MTR changes over time mirror the picture in
multiple sclerosis lesions, further validating MTR as a marker of tissue
integrity. Twenty-nine patients were recruited who had acute optic neuritis for
a median of 13 days (range 7-24 days) since the onset of visual symptoms. A
clinical examination and measurement of visual evoked potentials (VEP) was
performed on each patient. Their optic nerves were imaged with a fat-saturated
fast spin echo (FSE) sequence and a magnetization transfer sequence. Twenty-one
had multiple subsequent examinations over the course of 1 year. In addition, 27
control subjects had their optic nerves imaged up to three times over 1 year. A
blinded observer segmented the optic nerves from the MTR maps. Lesions were
defined on the acute FSE images and, from the coordinates, the ratio of mean
lesion MTR : healthy nerve MTR (lesion ratio) was calculated for each dataset.
The time-averaged mean MTR in control optic nerves was 47.7 per cent units (pu).
In diseased optic nerves, baseline mean MTR was 47.3 pu, with a mean lesion
ratio of 0.98. The diseased optic nerve MTR and lesion ratio declined over time
with a nadir at about 240 days at a mean MTR value of 44.2 pu and mean lesion
ratio of 0.91. Subsequently, diseased optic nerve MTR appeared to rise; after 1
year the diseased optic nerve mean MTR was 45.1 pu (mean lesion ratio 0.93),
although the difference was not significant compared with the nadir value. For
each 0.01 increase in time-averaged lesion ratio logMAR visual acuity recovery
improved by 0.03 (95% CI, 0.002, 0.08, P = 0.02). Time-averaged VEP central
field latency was shorter by 6.1 ms (95% CI 1.5, 10.7, P = 0.012) per 1 pu rise
in time-averaged diseased optic nerve MTR. The early fall in diseased optic
nerve MTR is consistent with demyelination and Wallerian degeneration of
transected axons. The late nadir compared with studies of multiple sclerosis
lesions may have been due to slow clearance of myelin debris. Remyelination may
have influenced subsequent MTR changes. The observations support using MTR to
monitor symptomatic demyelinating lesions.
PMID: 14736754 [PubMed]
71: Am J Physiol Endocrinol Metab. 2004 Jan 21 [Epub ahead of print]
Chronic C75 Treatment of Diet-Induced Obese Mice Increases Fat Oxidation and
Reduces Food Intake to Reduce Adipose Mass.
Thupari JN, Kim EK, Moran TH, Ronnett GV, Kuhajda FP.
Department of Pathology, The Johns Hopkins University School of Medicine,
Baltimore, MD, USA.
Obesity and its attendant disorders such as Type II diabetes are global health
problems. We previously reported that C75, an inhibitor of fatty acid synthase
(FAS) and stimulator of carnitine palmitoyltransferase-1 (CPT-1) caused anorexia
and profound weight loss in lean and genetically obese mice. To approximate
human obesity, we have utilized a chronic C75 treatment model for diet-induced
obese (DIO) mice. Chronic C75 treatment decreased food consumption and increased
energy expenditure due to increased fatty acid oxidation in both DIO and lean
mice. There was a substantial loss of adipose tissue and resolution of hepatic
steatosis in C75-treated DIO mice. Analysis of changes in the expression of
hypothalamic neuropeptides demonstrated that the reduced food consumption in
C75-treated DIO mice was accompanied by an increase in cocaine and
amphetamine-related transcript (CART) expression, not by changes in neuropeptide
Y (NPY) as seen with acute C75 treatment of lean mice. Inhibition of FAS and
stimulation of CPT-1 provide a means to achieve stable sustained weight loss in
DIO mice.
PMID: 14736702 [PubMed]
72: Eur J Appl Physiol. 2004 May;91(5-6):534-7. Epub 2004 Jan 21.
Influences of age and sex on abdominal muscle and subcutaneous fat thickness.
Kanehisa H, Miyatani M, Azuma K, Kuno S, Fukunaga T.
Department of Life Sciences (Sports Sciences), University of Tokyo, Komaba
3-8-1, Meguro-ku, 153-8902, Tokyo, Japan, hkane@idaten.c.u-tokyo.ac.jp
This study aimed to investigate the influences of age and sex on the thickness
of the rectus abdominis muscle and subcutaneous fat at the abdomen. The two
tissue thickness values were determined using ultrasonography in a total of 194
young (20-29 years) and elderly (70-79 years) persons of both genders. In both
sexes, the elderly groups showed significantly thinner muscle and thicker fat
than the younger groups. The percentage of the mean value of subcutaneous fat
thickness in the elderly group compared to that in the younger group was higher
in the women (176%) than in the men (128%), but the corresponding value of
muscle thickness was similar between men (68%) and women (65%). In both
generations, the women had significantly thinner muscle and thicker fat than the
men. The percentage of the mean value of subcutaneous fat thickness in the women
compared to that in the men was higher in the elderly group (169%) than in the
younger group (123%), but the corresponding value of muscle thickness was
similar between the younger (80%) and elderly (77%) groups. In every group,
subcutaneous fat thickness significantly correlated with waist circumference,
but muscle thickness did not. The findings here indicated that: (1) aging was
associated with a decrease of muscle thickness and an increase of subcutaneous
fat at the abdomen in men and women, with a similar relative loss of muscle
thickness in both genders and a greater increase of subcutaneous fat thickness
in women than in men, and (2) subcutaneous fat rather than muscle thickness
reflected waist circumference, regardless of age and gender.
PMID: 14735364 [PubMed]
73: Lipids. 2003 Nov;38(11):1157-65.
Genes regulated by arachidonic and oleic acids in Raji cells.
Verlengia R, Gorjao R, Kanunfre CC, Bordin S, de Lima TM, Newsholme P, Curi R.
Methodist University of Piracicaba, Faculty of Sciences of Health, Physical
Education, Sao Paulo, Brazil.
FA are known to modulate immune function in conditions such as arthritis and
lupus erythematosus. The effects of arachidonic (AA) and oleic acids (OA) on
function and pleiotropic gene expression of Raji cells were investigated. The
following parameters were evaluated: cytotoxicity as assessed by loss of
membrane integrity and DNA fragmentation; proliferation as measured by
[14C]thymidine incorporation; production of interleukin (IL)-10, interferon
(INF)-gamma, and tumor necrosis factor (TNF)-alpha; and expression of
pleiotropic genes by a macroarray technique (83 genes in total). AA was more
toxic to Raji cells than OA. Both FA promoted an increase in Raji cell
proliferation at 75 microM, whereas OA at high concentrations (200 microM)
decreased proliferation. AA reduced the production of IL-10, TNF-alpha, and
INF-gamma. On the other hand, OA provoked an increase of INF-gamma production
but did not affect the production of IL-10 and TNF-alpha. The proportions of
genes with altered expression were 27% for AA and 35% for OA. The FA affected
the expression of genes clustered as: cytokines, signal transduction pathways,
transcription factors, cell cycle, defense and repair, apoptosis, DNA synthesis,
cell adhesion, cytoskeleton, and hormone receptors. The most remarkable changes
were observed in the genes of signal transduction pathways. These results led us
to conclude that the effect of these FA on B-lymphocytes includes regulation of
gene expression. Thus, diets enriched with fat containing OA or AA may affect B
lymphocyte function in vivo.
PMID: 14733361 [PubMed]
74: J Am Podiatr Med Assoc. 2004 Jan-Feb;94(1):47-52.
Effects of changes in heel fat pad thickness and elasticity on heel pain.
Ozdemir H, Soyuncu Y, Ozgorgen M, Dabak K.
Department of Orthopaedics and Traumatology, Medical School of Akdeniz
University, Antalya, Turkey.
The heel fat pad has a unique structure that is important for its
shock-absorbing function. Loss of elasticity and changes in the thickness of the
heel pad have been suggested as causes of heel pain. The present study of a
population with heel pain shows the relationship between the thickness and
elasticity of the heel fat pad and age, sex, obesity, duration of symptoms,
subcalcaneal spurs, and noninvasive conservative treatment. Of 182 patients with
heel pain who visited an outpatient clinic during a 3-year period, 50 (67 heels)
fulfilling specific criteria were treated with a combination of nonsteroidal
anti-inflammatory drugs, contrast baths, stretching exercises, and change of
footwear habits. Patients were followed up for 1 year. Delayed healing,
increased thickness, and decreased elasticity of the heel fat pad were found in
patients who were older than 40 years, who had symptoms for longer than 12
months before treatment, and who had a large subcalcaneal spur. An increase in
heel fat pad thickness with aging and increased body weight reduce the
elasticity of the heel fat pad. In addition, subcalcaneal spurs diminish the
elasticity of the heel fat pad and play a role in the formation of heel pain.
PMID: 14729991 [PubMed]
75: Med Hypotheses. 2004;62(1):62-71.
A shift in myocardial substrate, improved endothelial function, and diminished
sympathetic activity may contribute to the anti-anginal impact of very-low-fat
diets.
McCarty MF.
Pantox Laboratories, 4622 Santa Fe St, San Diego, California 92109, USA.
mccarty@pantox.com
A new category of anti-anginal drug - exemplified by ranolazine - is believed to
work by partially inhibiting cardiac oxidation of fatty acids; oxidation of
glucose requires less oxygen per mol of ATP generated, and thus is preferable to
fat oxidation when oxygen availability is limiting in underperfused cardiac
tissue. Unfortunately, there is no reason to believe that these drugs inhibit
fat oxidation selectively in the heart; thus, chronic use of these drugs can be
expected to increase body fat stores until the original rate of fat oxidation is
restored by mass action - presumably negating the therapeutic benefit in angina,
while exacerbating the manifold adverse effects of insulin resistance syndrome.
The rational way to decrease cardiac metabolic reliance on fatty acids is to
consume a very-low-fat quasi-vegan diet (i.e., 10% fat calories). Indeed, such
diets are known to have a rapid and substantial therapeutic impact on anginal
symptoms, while concurrently benefiting insulin sensitivity, markedly improving
serum lipid profile, promoting leanness, and lessening coronary risk. A
reduction in diurnal insulin secretion might also be achieved, which would be
expected to decrease sympathetic activity. While reduced myocardial demand for
oxygen doubtless contributes to the beneficial impact of such diets on angina,
it is likely that improved cardiac perfusion consequent to improved
endothelium-dependent vasodilation also plays a role in this regard.
Supplemental carnitine, also beneficial in angina, appears to improve
utilization of glucose in the ischemic myocardium by lowering elevated
acetyl-coA levels and thereby disinhibiting pyruvate dehydrogenase. Certain
other nutraceuticals may aid control of angina by improving endothelial
function. In the longer term, these measures have the potential to slow or
reverse the progression of stenotic lesions that underlie most cases of angina.
These safe and relatively inexpensive nutritional strategies for coping with
angina deserve far more attention than orthodox medical practice has thus far
accorded them.
PMID: 14729006 [PubMed]
76: Am J Cardiovasc Drugs. 2002;2(4):245-53.
Pharmacotherapy of obesity: currently marketed and upcoming agents.
Bays H, Dujovne C.
Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky,
USA.
In many industrialized nations, obesity is now considered an epidemic, resulting
in accelerated morbidity and mortality. Obesity is associated with an increased
risk of coronary artery disease as well as the metabolic syndrome comprising
abdominal obesity, increased fasting blood glucose levels, dyslipidemia and
hypertension, which are all recognized cardiovascular risk factors. Diet,
exercise, and lifestyle changes constitute important recommendations for
treatment. Unfortunately, although effective in some individuals, these
recommendations have proven to be ineffective in adequately addressing the
broad, enlarging scope of this public health problem. Drug treatment is often
indicated but is somewhat limited by the minimal number of well tolerated drugs
that have proven to have long-term efficacy in maintaining bodyweight loss. For
example, phentermine may result in modest bodyweight loss through suppression of
appetite, but potential cardiovascular adverse effects exist and the efficacy is
mainly short-term. Sibutramine, an inhibitor of serotonin and norepinephrine
(noradrenaline) reuptake, may increase satiety and result in modest bodyweight
loss. However, cardiovascular adverse effects may occur in susceptible patients.
Nonetheless, sibutramine is one of the few drugs that has been approved by the
US Food and Drug Administration (FDA) for bodyweight loss. Orlistat, a lipase
inhibitor, is also approved by the FDA for bodyweight loss but may have
bothersome gastrointestinal adverse effects, especially among patients who do
not adhere to the recommended low-fat diet. Ongoing studies continue to evaluate
other drug treatments that may result in bodyweight reduction through a number
of different mechanisms. It is anticipated that the development of effective and
well tolerated antiobesity drugs will elevate the pharmacologic treatment of
obesity to the status of other cardiovascular risk factors and metabolic
disorders. This may be especially important given that dyslipidemia,
hypertension and type 2 diabetes mellitus are often secondary to, or exacerbated
by, obesity.
Publication Types:
Review
Review, Tutorial
PMID: 14727970 [PubMed]
77: EMBO J. 2004 Jan 28;23(2):386-95. Epub 2004 Jan 15.
Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory
protein 2 dominates iron homeostasis.
Meyron-Holtz EG, Ghosh MC, Iwai K, LaVaute T, Brazzolotto X, Berger UV, Land W,
Ollivierre-Wilson H, Grinberg A, Love P, Rouault TA.
Cell Biology and Metabolism Branch, Bethesda, MD, USA.
The two iron regulatory proteins IRP1 and IRP2 bind to transcripts of ferritin,
transferrin receptor and other target genes to control the expression of iron
metabolism proteins at the post-transcriptional level. Here we compare the
effects of genetic ablation of IRP1 to IRP2 in mice. IRP1-/- mice misregulate
iron metabolism only in the kidney and brown fat, two tissues in which the
endogenous expression level of IRP1 greatly exceeds that of IRP2, whereas
IRP2-/- mice misregulate the expression of target proteins in all tissues.
Surprisingly, the RNA-binding activity of IRP1 does not increase in animals on a
low-iron diet that is sufficient to activate IRP2. In animal tissues, most of
the bifunctional IRP1 is in the form of cytosolic aconitase rather than an
RNA-binding protein. Our findings indicate that the small RNA-binding fraction
of IRP1, which is insensitive to cellular iron status, contributes to basal
mammalian iron homeostasis, whereas IRP2 is sensitive to iron status and can
compensate for the loss of IRP1 by increasing its binding activity. Thus, IRP2
dominates post-transcriptional regulation of iron metabolism in mammals.
PMID: 14726953 [PubMed]
78: Endocrinol Metab Clin North Am. 2003 Dec;32(4):935-65.
Medical nutrition therapy for the treatment of obesity.
Plodkowski RA, St Jeor ST.
Endocrinology and Metabolism Service, Reno Veterans Affairs Medical Center, 1000
Locust Street, Mailstop 111, Reno, NV 89502, USA. rayp@med.unr.edu
Most physicians do not have the benefit of in-house registered dietitians to
facilitate patient evaluation and create treatment plans. Fortunately, with the
new tools that are available to physicians and patients, energy balance can be
evaluated. Then, a balanced deficit diet can be encouraged to achieve a weight
management goal while maintaining healthy food intake patterns. Patients should
also be counseled regarding weight maintenance diets to prevent weight gain. A
low-fat diet is preferred because the patient will benefit from improved cardiac
risk as a result of weight loss and a restricted saturated fat content is
healthier. Other diets and approaches are acceptable if they are hypocaloric and
do not negatively impact the patient's health (eg, some high-protein, high-fat
diets can increase lipid levels; high-carbohydrate diets can increase
triglycerides in patients who have type 2 diabetes). As patients lose weight,
further increases in physical activity and exercise should be emphasized to help
maintain lost weight. It is also helpful from a behavioral perspective to
encourage patients to monitor their weight, food intake, and physical activity.
Medical offices can support patients by providing weekly or biweekly weigh-ins
to track progress and provide ongoing feedback. Patients should be reminded that
the ultimate goal of any weight management program is gradual, incremental
weight losses that are maintained over time. Sustainable and enjoyable changes
in eating practices and physical activity patterns must be made along with a
lifelong commitment to health.
Publication Types:
Review
Review, Tutorial
PMID: 14711069 [PubMed]
79: Int J Obes Relat Metab Disord. 2004 Jan;28(1):57-64.
High protein intake sustains weight maintenance after body weight loss in
humans.
Westerterp-Plantenga MS, Lejeune MP, Nijs I, van Ooijen M, Kovacs EM.
Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
M.Westerterp@HB.UNIMAAS.NL
BACKGROUND: A relatively high percentage of energy intake as protein has been
shown to increase satiety and decrease energy efficiency during overfeeding.
AIM: To investigate whether addition of protein may improve weight maintenance
by preventing or limiting weight regain after weight loss of 5-10% in moderately
obese subjects. DESIGN OF THE STUDY: In a randomized parallel design, 148 male
and female subjects (age 44.2 +/- 10.1 y; body mass index (BMI) 29.5 +/- 2.5
kg/m2; body fat 37.2 +/- 5.0%) followed a very low-energy diet (2.1 MJ/day)
during 4 weeks. For subsequent 3 months weight-maintenance assessment, they were
stratified according to age, BMI, body weight, restrained eating, and resting
energy expenditure (REE), and randomized over two groups. Both groups visited
the University with the same frequency, receiving the same counseling on demand
by the dietitian. One group (n=73) received 48.2 g/day additional protein to
their diet. Measurements at baseline, after weight loss, and after 3 months
weight maintenance were body weight, body composition, metabolic measurements,
appetite profile, eating attitude, and relevant blood parameters. RESULTS:
Changes in body mass, waist circumference, REE, respiratory quotient (RQ), total
energy expenditure (TEE), dietary restraint, fasting blood-glucose, insulin,
triacylglycerol, leptin, beta-hydroxybutyrate, glycerol, and free fatty acids
were significant during weight loss and did not differ between groups. During
weight maintenance, the 'additional-protein group' showed in comparison to the
nonadditional-protein group 18 vs 15 en% protein intake, a 50% lower body weight
regain only consisting of fat-free mass, a 50% decreased energy efficiency,
increased satiety while energy intake did not differ, and a lower increase in
triacylglycerol and in leptin; REE, RQ, TEE, and increases in other blood
parameters measured did not differ. CONCLUSION: A 20% higher protein intake,
that is, 18% of energy vs 15% of energy during weight maintenance after weight
loss, resulted in a 50% lower body weight regain, only consisting of fat-free
mass, and related to increased satiety and decreased energy efficiency.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14710168 [PubMed]
80: Med Sci Sports Exerc. 2004 Jan;36(1):137-42.
Annual changes of bone density over 12 years in an amenorrheic athlete.
Zanker CL, Cooke CB, Truscott JG, Oldroyd B, Jacobs HS.
School of Leisure and Sport Studies, Leeds Metropolitan University, UK.
c.zanker@lmu.ac.uk
PURPOSE: To link annual changes of bone mineral density (BMD) over 12
consecutive years to pharmacological intervention and to fluctuations of body
mass and body composition in an amenorrheic athlete. METHODS: BMD of the lumbar
spine (LS) and total proximal femur (PF) were measured using dual energy x-ray
absorptiometry (DXA), every 11-13 months between ages 24.8 and 36.9 yr. Body
composition was assessed every 3-4 yr from a whole body DXA scan. Body mass was
recorded every 3 months. For the first 5 yr of study, the subject used oral
contraceptives (OC). For the subsequent 7 yr, she used estradiol skin patches
(EP) with oral norethisterone. RESULTS: The first DXA scan (age 24.8 yr)
revealed a low BMD at both LS and PF, with T-scores of -1.4 and -2.8,
respectively. During the next 5 yr, while adhering to OC, the BMD of her LS and
PF declined by 9.8% and 12.1%, respectively. Concomitantly, her body mass fell
from 45.1 to 41.4 kg, her body mass index (BMI) from 16.4 to 15.0 kg.m-2, and
her percent body fat from 8.3 to <4.0%. While treated with EP and norethisterone
(age 29.8-33.5 yr), her LS BMD gradually increased by 9.4%, despite a further
0.8 kg decline of body mass. From age 33.8 to 36.9 yr, voluntary weight gain
(2-3 kg.yr-1; total: 8.1 kg) was accompanied by an increase of her PF BMD
(16.9%), with no further increase at the LS. CONCLUSION: Changes of BMD at the
total proximal femur reflected changes of body mass in this subject. At the
lumbar spine, BMD declined with weight loss but increased in association with
transdermal estradiol treatment in the absence of weight gain.
PMID: 14707779 [PubMed]
81: Peptides. 2003 Oct;24(10):1545-51.
Lipid metabolism in the cockroach, Periplaneta americana, is activated by the
hypertrehalosemic peptide, HTH-I.
Oguri E, Steele JE.
Department of Biology, The University of Western Ontario, Ont., N6A 5B7, London,
Canada.
Phosphatidylcholine and phosphatidylethanolamine are the major constituents of
the phospholipid pool in cockroach (Periplaneta americana) fat body and
hemolymph. Both species of phospholipid are significantly decreased 6h after
injecting hypertrehalosemic hormone I (HTH-I) into the hemocoel. Loss of
phospholipid is accompanied by an accumulation of the phospholipid degradation
products glycerophosphorylcholine and glycerol. HTH-I also increases
phospholipase activity in the hemolymph and this is thought to be responsible
for the depletion of hemolymph phospholipid. Phospholipase activity peaks
approximately 2h after injection of HTH-I and returns to normal at 6h. In vitro,
total phospholipid in the fat body is decreased by HTH-I whereas the
concentration of diacylglycerol displays a corresponding increase. HTH-I
elevates free fatty acid levels but has no effect on triacylglycerol. These
effects of HTH-I are blocked by the phospholipase inhibitor mepacrine.
PMID: 14706533 [PubMed]
82: Int J Obes Relat Metab Disord. 2003 Dec;27 Suppl 3:S6-11.
Cellular mechanism of insulin resistance: potential links with inflammation.
Perseghin G, Petersen K, Shulman GI.
Internal Medicine-Section of Nutrition/Metabolism and Unit of Clinical
Spectroscopy, Istituto Scientifico H San Raffaele via Olgettina 60, Milan,
Italy.
Insulin resistance is a pivotal feature in the pathogenesis of type 2 diabetes,
and it may be detected 10-20 y before the clinical onset of hyperglycemia.
Insulin resistance is due to the reduced ability of peripheral target tissues to
respond properly to insulin stimulation. In particular, impaired
insulin-stimulated muscle glycogen synthesis plays a significant role in insulin
resistance. Glucose transport (GLUT4), phosphorylation (hexokinase) and storage
(glycogen synthase) are the three potential rate-controlling steps regulating
insulin-stimulated muscle glucose metabolism, and all three have been implicated
as being the major defects responsible for causing insulin resistance in
patients with type 2 diabetes. Using (13)C/(31)P magnetic resonance spectroscopy
(MRS), we demonstrate that a defect in insulin-stimulated muscle glucose
transport activity is the rate-controlling defect. Using a similar (13)C/(31)P
MRS approach, we have also demonstrated that fatty acids cause insulin
resistance in humans due to a decrease in insulin-stimulated muscle glucose
transport activity, which could be attributed to reduced insulin-stimulated
IRS-1-associated phosphatidylinositol 3-kinase activity, a required step in
insulin-stimulated glucose transport into muscle. Furthermore, we have recently
proposed that this defect in insulin-stimulated muscle glucose transport
activity may be due to the activation of a serine kinase cascade involving
protein kinase C theta and IKK-beta, which are key downstream mediators of
tissue inflammation. Finally, we propose that any perturbation that leads to an
increase in intramyocellular lipid (fatty acid metabolites) content such as
acquired or inherited defects in mitochondrial fatty acid oxidation, defects in
adipocyte fat metabolism or simply increased fat delivery to muscle/liver due to
increased energy intake will lead to insulin resistance through this final
common pathway. Understanding these key cellular mechanisms of insulin
resistance should help elucidate new targets for treating type 2 diabetes.
Publication Types:
Review
Review, Tutorial
PMID: 14704736 [PubMed]
83: J Nutr. 2004 Jan;134(1):99-103.
Iron supplementation does not affect the susceptibility of LDL to oxidative
modification in women with low iron status.
Binkoski AE, Kris-Etherton PM, Beard JL.
Graduate Program in Nutrition, The Department of Nutritional Sciences, The
Pennsylvania State University, University Park, PA, USA.
Elevated iron stores may or may not promote atherogenesis by increasing free
radical formation and oxidative stress, but controlled diet and supplement
trials are lacking. We tested the hypothesis that iron supplementation does not
increase the susceptibility of LDL to undergo oxidative modification in women
with low iron status. A randomized, double-blind, 2-period crossover study
design (n=26) was used to examine the effects of the following diets on measures
of LDL oxidation: average American diet (AAD) [36% of energy as fat; 15%
saturated fatty acids (SFA)], and a Step 2 diet (26% fat; 7% SFA). In addition,
subjects received either a supplement containing 160 mg of ferrous sulfate (50
mg elemental iron) or a placebo twice daily [supplement group received a total
of 320 mg ferrous sulfate (100 mg elemental iron) daily]. After supplementation,
serum ferritin differed between the supplement and placebo groups (P=0.008).
Measures of LDL oxidation were not affected by supplement intake; however, they
were affected by diet. Lag time was shorter after the women consumed the AAD
diet than after the Step 2 diet (P<0.0001). The diets did not affect the rate of
oxidation or total dienes. Although iron status was improved by aggressive iron
supplementation, LDL oxidative susceptibility was not affected. As expected, lag
time was increased after the women consumed the low fat, low SFA diet.
Therefore, the results of this study do not support a relationship between iron
status and LDL oxidation.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14704300 [PubMed]
84: J Nutr Sci Vitaminol (Tokyo). 2003 Oct;49(5):320-6.
Effect of dietary fat level and sesamin on the polyunsaturated fatty acid
metabolism in rats.
Mizukuchi A, Umeda-Sawada R, Igarashi O.
Institute of Environmental Science for Human Life, Ochanomizu University, 2-1-1,
Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
In this study, we examined the effects of sesamin and vegetable oil on the
concentrations of polyunsaturated fatty acid (PUFA) and lipids (triacylglycerol,
free cholesterol, and phospholipid), and beta-oxidation enzyme activities in the
rat liver. Rats were fed a diet containing 5% (low-fat diet) or 20% (high-fat
diet) salad oil (rapeseed oil: soybean oil, 7:3) with or without sesamin (0.5%
w/w) for 4 wk. As a result, the concentrations of linoleic acid (LA, n-6),
alpha-linolenic acid (ALA, n-3), and total PUFA in the liver increased
significantly as the result of the high-fat diet. In the high-fat diet groups,
sesamin administration decreased the concentrations of LA, ALA, and total PUFA
to almost the same level as the low-fat diet group, while it increased the
concentrations of dihomo-gamma-linolenic acid (DGLA, n-6) and arachidonic acid
(AA, n-6). The activities of carnitine acyltransferase and acyl-CoA
dehydrogenase in liver mitochondria were enhanced by the intake of the high-fat
diet, and were further enhanced by the administration of sesamin. Peroxisomal
acyl-CoA oxidase activity was also enhanced by sesamin, while it was not
affected by the dietary fat level. These results suggest that sesamin suppressed
the increase of hepatic PUFA concentration caused by feeding the high-fat diet
through enhancing the enzyme activities of fatty acid beta-oxidation and PUFA
metabolism from LA and ALA.
PMID: 14703306 [PubMed]
85: Br J Psychiatry. 2004 Jan;184:58-62.
Effects of antipsychotics on fat deposition and changes in leptin and insulin
levels. Magnetic resonance imaging study of previously untreated people with
schizophrenia.
Zhang ZJ, Yao ZJ, Liu W, Fang Q, Reynolds GP.
Department of Psychiatry Nanjing Brain Hospital and Nanjing Medical University,
Nanjing, China.
BACKGROUND: Weight gain is a common consequence of antipsychotic drug treatment
and can lead to further morbidity. AIMS: To assess the effects of antipsychotic
drug therapy on abdominal fat deposition, on insulin and leptin secretion, and
on circulating glucose and lipids. METHOD: Abdominal body fat was determined by
magnetic resonance imaging in a group of previously untreated patients with
schizophrenia, before and after 10 weeks' antipsychotic drug treatment. Body
mass and blood concentrations of glucose, insulin, leptin and lipids were also
measured. RESULTS: Significant increases in both subcutaneous and
intra-abdominal fat were identified after antipsychotic drug treatment. A
three-fold increase in leptin secretion as well as significant increases in
levels of circulating lipids and non-fasting glucose were also identified.
CONCLUSIONS: Patients first receiving antipsychotic drugs experience substantial
deposition of both subcutaneous and intra-abdominal fat, reflecting a loss of
the normal inhibitory control of leptin on body mass. Along with fat deposition,
the increase in levels of fasting lipids and in non-fasting glucose may provide
early signs of drug-induced progression towards the metabolic syndrome.
PMID: 14702228 [PubMed]
86: Obes Res. 2003 Dec;11(12):1509-18.
Prior exercise increases dietary oleate, but not palmitate oxidation.
Votruba SB, Atkinson RL, Schoeller DA.
Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin
53706, USA.
OBJECTIVE: Higher levels of physical activity have been associated with body
weight maintenance, but previous work in our laboratory suggests that this is
not purely related to energy balance. We hypothesize that this may be related to
the partitioning of dietary fat between oxidation and storage. RESEARCH METHODS
AND PROCEDURES: Healthy women (age 24 +/- 1 years, BMI = 21.2 +/- 0.4 kg/m2)
were recruited to participate in rest (n = 10) or exercise sessions of light (n
= 11), moderate (n = 10), and heavy (n = 7) exercise. All exercises (1250 kJ
above rest) were performed on a stationary cycle inside of a whole-body
calorimeter. [1-(13)C]oleate and [d31]palmitate were given in a liquid meal 30
minutes post-exercise. An additional study was done with identical exercise
sessions, but with administration of an oral dose of [1-(13)C]acetate and
[d3]acetate 30 minutes post-exercise to determine label sequestration. RESULTS:
Cumulative oxidation of [1-(13)C]oleate was significantly greater after light
(45 +/- 3%), moderate (54 +/- 4%), and heavy (51 +/- 4%) exercise than that with
rest (33 +/- 3%) (p = 0.0008). Cumulative oxidation of [d31]palmitate did not
differ among trials (12 +/- 2%, 14 +/- 1%, 17 +/- 2%, and 14 +/- 2% for rest,
light, moderate, and heavy, respectively; p = 0.30). DISCUSSION: Exercise
standardized for energy expenditure increases monounsaturated fat oxidation more
than saturated fat oxidation and that the increase occurs regardless of
intensity. Recommendations for physical activity for the purposes of weight
control may be specific for dietary fat composition.
PMID: 14694216 [PubMed]
87: Obes Res. 2003 Dec;11(12):1471-9.
Dietary regulation of fat oxidative gene expression in different skeletal muscle
fiber types.
McAinch AJ, Lee JS, Bruce CR, Tunstall RJ, Hawley JA, Cameron-Smith D.
School of Health Sciences, Deakin University, Burwood, Victoria, Australia.
OBJECTIVE: To determine the effect of a high-fat diet on the expression of genes
important for fat oxidation, the protein abundance of the transcription factors
peroxisome proliferator-activated receptor (PPAR) isoforms alpha and gamma, and
selected enzyme activities in type I and II skeletal muscle. RESEARCH METHODS
AND PROCEDURES: Sprague-Dawley rats consumed either a high-fat (HF: 78% energy,
n = 8) or high-carbohydrate (64% energy, n = 8) diet for 8 weeks while remaining
sedentary. RESULTS: The expression of genes important for fat oxidation tended
to increase in both type I (soleus) and type II (extensor digitorum longus)
fiber types after an HF dietary intervention. However, the expression of muscle
type carnitine palmitoyltransferase I was not increased in extensor digitorum
longus. Analysis of the gene expression of both peroxisome
proliferator-activated receptor-gamma coactivator and fork-head transcription
factor O1 demonstrated no alteration in response to the HF diet. Similarly,
PPARalpha and PPARgamma protein levels were also not altered by the HF diet.
DISCUSSION: An HF diet increased the expression of an array of genes involved in
lipid metabolism, with only subtle differences evident in the response within
differing skeletal muscle fiber types. Despite changes in gene expression, there
were no effects of diet on peroxisome proliferator-activated receptor-gamma
coactivator and fork-head transcription factor O1 mRNA and the protein abundance
of PPARalpha and PPARgamma.
PMID: 14694211 [PubMed]
88: Am J Physiol Endocrinol Metab. 2004 May;286(5):E737-43. Epub 2003 Dec 23.
Intensified exercise training does not alter AMPK signaling in human skeletal
muscle.
Clark SA, Chen ZP, Murphy KT, Aughey RJ, McKenna MJ, Kemp BE, Hawley JA.
Exercise Metabolism Group, School of Medical Sciences, RMIT University, PO Box
71, Bundoora, Victoria 3083, Australia.
The AMP-activated protein kinase (AMPK) cascade has been linked to many of the
acute effects of exercise on skeletal muscle substrate metabolism, as well as to
some of the chronic training-induced adaptations. We determined the effect of 3
wk of intensified training (HIT; 7 sessions of 8 x 5 min at 85% Vo2 peak) in
skeletal muscle from well-trained athletes on AMPK responsiveness to exercise.
Rates of whole body substrate oxidation were determined during a 90-min
steady-state ride (SS) pre- and post-HIT. Muscle metabolites and AMPK signaling
were determined from biopsies taken at rest and immediately after exercise
during the first and seventh HIT sessions, performed at the same (absolute)
pre-HIT work rate. HIT decreased rates of whole body carbohydrate oxidation (P <
0.05) and increased rates of fat oxidation (P < 0.05) during SS. Resting muscle
glycogen and its utilization during intense exercise were unaffected by HIT.
However, HIT induced a twofold decrease in muscle [lactate] (P < 0.05) and
resulted in tighter metabolic regulation, i.e., attenuation of the decrease in
the PCr/(PCr + Cr) ratio and of the increase in [AMPfree]/ATP. Resting
activities of AMPKalpha1 and -alpha2 were similar post-HIT, with the magnitude
of the rise in response to exercise similar pre- and post-HIT. AMPK
phosphorylation at Thr172 on both the alpha1 and alpha2 subunits increased in
response to exercise, with the magnitude of this rise being similar post-HIT.
Acetyl-coenzyme A carboxylase-beta phosphorylation was similar at rest and,
despite HIT-induced increases in whole body rates of fat oxidation, did not
increase post-HIT. Our results indicate that, in well-trained individuals,
short-term HIT improves metabolic control but does not blunt AMPK signaling in
response to intense exercise.
PMID: 14693511 [PubMed]
89: Proc Nutr Soc. 2003 Aug;62(3):663-6.
Energy expenditure, physical activity and body-weight control.
Tappy L, Binnert C, Schneiter P.
Institute of Physiology, University of Lausanne, 7 rue du Bugnon, 1005 Lausanne,
Switzerland. Luc.Tappy@iphysiol.unil.ch
Regular physical exercise and endurance training are associated with low body
weight and low body fat mass. The relationship between exercise and body-weight
control is complex and incompletely understood. Regular exercise may decrease
energy balance through an increase in energy expenditure or an increase in fat
oxidation. It may also contribute to weight loss by modulating nutrient intake.
An intriguing question that remains unresolved is whether changes in nutrient
intake or body composition secondarily affect spontaneous physical activity. If
this were the case, physical activity would represent a major adaptative
mechanism for body-weight control.
Publication Types:
Review
Review, Tutorial
PMID: 14692602 [PubMed]
90: Am J Physiol Endocrinol Metab. 2004 Apr;286(4):E615-20. Epub 2003 Dec 16.
Retention of estradiol negative feedback relationship to LH predicts ovulation
in response to caloric restriction and weight loss in obese patients with
polycystic ovary syndrome.
van Dam EW, Roelfsema F, Veldhuis JD, Hogendoorn S, Westenberg J, Helmerhorst
FM, Frolich M, Krans HM, Meinders AE, Pijl H.
Department of General Internal Medicine, Leiden University Medical Center,
C1-R39, 2300 RC Leiden, The Netherlands.
The present study tests the hypothesis that specific endocrine, metabolic, and
anthropometric features distinguish obese women with polycystic ovary syndrome
(PCOS) who resume ovulation in response to calorie restriction and weight loss
from those who do not. Fifteen obese (body mass index 39 +/- 7 kg/m(2))
hyperandrogenemic oligoovulatory patients undertook a very low calorie diet
(VLCD), wherein each lost > or =10% of body weight over a mean of 6.25 mo. Body
fat distribution was quantitated by magnetic resonance imaging. Hormones were
measured in the morning at baseline, after 1 wk of VLCD, and after 10% weight
loss. To monitor LH release, blood was sampled for 24 h at 10-min intervals
before intervention and after 7 days of VLCD. Responders were defined a priori
as individuals exhibiting two or more ovulatory cycles in the course of
intervention, as corroborated by serum progesterone concentrations > or =18
nmol/l followed by vaginal bleeding. At baseline, responders had a higher sex
hormone-binding globulin (SHBG) concentration but were otherwise
indistinguishable from nonresponders. Body weight, the size of body fat depots,
and plasma insulin levels declined to a similar extent in responders and
nonresponders. Also, SHBG increased, and the free testosterone index decreased
comparably. However, responders exhibited a significant decline of circulating
estradiol concentrations (from 191 +/- 82 to 158 +/- 77 pmol/l, means +/- SD, P
= 0.037) and a concurrent increase in LH secretion (from 104 +/- 42 to 140 +/- 5
U.l(-1).day(-1), P = 0.006) in response to 7 days of VLCD, whereas neither
parameter changed significantly in nonresponders. We infer that evidence of
retention of estradiol-dependent negative feedback on LH secretion may forecast
follicle maturation and ovulation in obese patients with PCOS under dietary
restriction.
PMID: 14678951 [PubMed]
91: Mol Cell Biochem. 2003 Dec;254(1-2):339-46.
Dose- and time-dependent effects of a novel (-)-hydroxycitric acid extract on
body weight, hepatic and testicular lipid peroxidation, DNA fragmentation and
histopathological data over a period of 90 days.
Shara M, Ohia SE, Yasmin T, Zardetto-Smith A, Kincaid A, Bagchi M, Chatterjee A,
Bagchi D, Stohs SJ.
Department of Pharmacy Sciences, School of Pharmacy and Health Professions,
Creighton University Medical Center, Omaha, NE 68178, USA.
(-)-Hydroxycitric acid (HCA), a natural extract from the dried fruit rind of
Garcinia cambogia (family Guttiferae), is a popular supplement for weight
management. The dried fruit rind has been used for centuries as a condiment in
Southeastern Asia to make food more filling and satisfying. A significant number
of studies highlight the efficacy of Super CitriMax (HCA-SX, a novel 60%
calcium-potassium salt of HCA derived from Garcinia cambogia) in weight
management. These studies also demonstrate that HCA-SX promotes fat oxidation,
inhibits ATP-citrate lyase (a building block for fat synthesis), and lowers the
level of leptin in obese subjects. Acute oral, acute dermal, primary dermal
irritation and primary eye irritation toxicity studies have demonstrated the
safety of HCA-SX. However, no long-term safety of HCA-SX or any other
(-)-hydroxycitric acid extract has been previously assessed. In this study, we
have evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley
rats on body weight, hepatic and testicular lipid peroxidation, DNA
fragmentation, liver and testis weight, expressed as such and as a % of body
weight and brain weight, and histopathological changes over a period of 90 days.
The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX as feed intake and the
animals were sacrificed on 30, 60 or 90 days of treatment. The feed and water
intake were assessed and correlated with the reduction in body weight. HCA-SX
supplementation demonstrated a reduction in body weight in both male and female
rats over a period of 90 days as compared to the corresponding control animals.
An advancing age-induced marginal increase in hepatic lipid peroxidation was
observed in both male and female rats as compared to the corresponding control
animals. However, no such difference in hepatic DNA fragmentation and testicular
lipid peroxidation and DNA fragmentation was observed. Furthermore, liver and
testis weight, expressed as such and as a percentage of body weight and brain
weight, at 30, 60 and 90 days of treatment, exhibited no significant difference
between the four groups. Taken together, these results indicate that treatment
of HCA-SX over a period of 90 days results in a reduction in body weight, but
did not cause any changes in hepatic and testicular lipid peroxidation, DNA
fragmentation, or histopathological changes.
PMID: 14674714 [PubMed]
92: Mol Cell Biol. 2004 Jan;24(1):320-9.
p50alpha/p55alpha phosphoinositide 3-kinase knockout mice exhibit enhanced
insulin sensitivity.
Chen D, Mauvais-Jarvis F, Bluher M, Fisher SJ, Jozsi A, Goodyear LJ, Ueki K,
Kahn CR.
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard
Medical School, Boston, Massachusetts 02215, USA.
Class Ia phosphoinositide (PI) 3-kinases are heterodimers composed of a
regulatory and a catalytic subunit and are essential for the metabolic actions
of insulin. In addition to p85alpha and p85beta, insulin-sensitive tissues such
as fat, muscle, and liver express the splice variants of the pik3r1 gene,
p50alpha and p55alpha. To define the role of these variants, we have created
mice with a deletion of p50alpha and p55alpha by using homologous recombination.
These mice are viable, grow normally, and maintain normal blood glucose levels
but have lower fasting insulin levels. Results of an insulin tolerance test
indicate that p50alpha/p55alpha knockout mice have enhanced insulin sensitivity
in vivo, and there is an increase in insulin-stimulated glucose transport in
isolated extensor digitorum longus muscle tissues and adipocytes. In muscle,
loss of p50alpha/p55alpha results in reduced levels of insulin-stimulated
insulin receptor substrate 1 (IRS-1) and phosphotyrosine-associated PI 3-kinase
but enhanced levels of IRS-2-associated PI 3-kinase and Akt activation, whereas
in adipocytes levels of both insulin-stimulated PI 3-kinase and Akt are
unchanged. Despite this, adipocytes of the knockout mice are smaller and have
increased glucose uptake with altered glucose metabolic pathways. When treated
with gold thioglucose, p50alpha/p55alpha knockout mice become hyperphagic like
their wild-type littermates. However, they accumulate less fat and become mildly
less hyperglycemic and markedly less hyperinsulinemic. Taken together, these
data indicate that p50alpha and p55alpha play an important role in insulin
signaling and action, especially in lipid and glucose metabolism.
PMID: 14673165 [PubMed]
93: J Nutr. 2003 Nov;133(11 Suppl 2):3893S-3897S.
Animal source foods and human health during evolution.
Larsen CS.
Department of Anthropology, The Ohio State University, Columbus, OH, USA.
Larsen.53@osu.edu
Animal source foods (ASF) have always been a constituent of human diets. Their
pattern of use, however, changed in dramatic ways over the course of human
evolution. Before 2 million years ago (mya), meat in particular was acquired
opportunistically via hunting of small or young animals and scavenging of
animals killed by other species. At some point after that time, humans began to
hunt cooperatively, making possible the acquisition of meat from large game. The
marked increase in human heights between 2.0 and 1.7 mya may be linked to more
efficient means of acquiring meat, namely through hunting. The final pattern of
meat (and other ASF) use before the modern era is associated with the shift from
hunting and gathering beginning approximately 10,000 y ago. This fundamental
dietary change resulted in a narrowing of diet, reduced consumption of meat and
increased focus on domesticated grains. The study of archaeological human
remains from around the world reveals that this period in human dietary history
saw a decline in health, including increased evidence of morbidity (poorer
dental health, increased occlusal abnormalities, increased iron deficiency
anemia, increased infection and bone loss). Human populations living in
developing and developed settings today rely on meats with lipid compositions
that when eaten in excess promote cardiovascular disease. As humans become more
sedentary and eat more high fat foods, we can expect to see increases in heart
disease, osteoporosis and other diseases of "civilization."
Publication Types:
Review
Review, Tutorial
PMID: 14672287 [PubMed]
94: J Clin Endocrinol Metab. 2003 Dec;88(12):5827-33.
Short- and long-term effects of growth hormone (GH) replacement on protein
metabolism in GH-deficient adults.
Shi J, Sekhar RV, Balasubramanyam A, Ellis K, Reeds PJ, Jahoor F, Sharma MD.
Department of Medicine, Children's Nutrition Research Center, Baylor College of
Medicine, Houston, Texas 77030, USA.
Reduced fat-free mass (FFM) in GH-deficient (GHD) adults is improved by GH
replacement, but the protein metabolic changes are unclear. Using iv
[(2)H(3)]leucine and oral l-[(13)C(1)]leucine infusions and dual emission x-ray
absorptiometry, we compared leucine kinetics and body composition in eight GHD
adults and eight healthy controls in the fasted and fed states, before and after
2 wk and 6 months of GH replacement. Leucine kinetics were not different between
pretreatment GHD subjects and controls. After 2 wk of GH treatment, leucine
oxidation decreased in the GHD subjects compared with baseline values [fasted,
41 +/- 6 vs. 30 +/- 5 micromol/kg FFM.h (P < 0.01); fed, 49 +/- 3 vs. 41 +/- 3.6
micromol/kg FFM.h (P < 0.05)], leucine balance improved [fasted, -14 +/- 4 vs.
-3.5 +/- 3 micromol/kg FFM.h (P < 0.01); fed, 65 +/- 10 vs. 72 +/- 7 micromol/kg
FFM.h (P = 0.07)], and protein synthesis increased [fasted, 116 +/- 5 vs. 131
+/- 6 micromol/kg FFM.h (P < 0.05); fed, 103 +/- 6 vs. 116 +/- 6 micromol/kg
FFM.h (P < 0.05)]. After 6 months of GH treatment, these changes were not
maintained in the fed state. The five GHD subjects with decreased FFM at
baseline showed a significant increase after 6 months of GH treatment (P <
0.05). GH replacement in GHD acutely improves protein balance by stimulating
synthesis and inhibiting catabolism. After 6 months, protein kinetics reached a
new homeostasis to maintain the net gain in FFM.
PMID: 14671176 [PubMed]
95: Circ Res. 2004 Feb 6;94(2):239-44. Epub 2003 Dec 11.
Cerebral microvascular responses to hypercholesterolemia: roles of NADPH oxidase
and P-selectin.
Ishikawa M, Stokes KY, Zhang JH, Nanda A, Granger DN.
Department of Molecular and Cellular Physiology, Louisiana State University
Health Sciences Center, Shreveport, La 71130-3932, USA.
Although hypercholesterolemia is widely accepted as a major risk factor for
coronary artery and peripheral vascular diseases, its role in the pathogenesis
of stroke is controversial. The objectives of this study were to determine how
hypercholesterolemia affects the cerebral microcirculation under resting
conditions and after ischemia-reperfusion (I/R). Platelet- and
leukocyte-endothelial cell interactions and oxidant production (using the
oxidant-sensitive fluorochrome dihydrorhodamine-123) were monitored by
intravital videomicroscopy in the cerebral microvasculature of mice placed on
either a normal (ND) or cholesterol-enriched diet (HCD). Platelets labeled with
carboxyfluorescein diacetate succinimidyl ester (CFDASE) and leukocytes labeled
with rhodamine 6G were seen to roll and firmly adhere, with a corresponding
increase in oxidant production, in venules of mice on HCD, but not ND.
Immunoneutralization of P-selectin attenuated the platelet- and
leukocyte-endothelial cell interactions and the enhanced oxidant production
associated with HCD. A GPIIb/IIIa blocking antibody did not alter the blood
cell-vessel wall interactions to HCD. Mice deficient in the NADPH oxidase
subunit gp91(phox) exhibited significantly blunted platelet and leukocyte
recruitment responses to HCD. Focal I/R also elicited inflammatory and
prothrombogenic responses in cerebral venules and these were exaggerated in mice
on HCD. These results implicate an oxidant-dependent, P-selectin-mediated
mechanism in the blood cell-vessel wall interactions induced by
hypercholesterolemia in the brain and demonstrate that the deleterious effects
of I/R on the brain are exacerbated by this cardiovascular risk factor.
PMID: 14670846 [PubMed]
96: Int J Sport Nutr Exerc Metab. 2003 Sep;13(3):286-93.
Case study of training, fitness, and nourishment of a dog driver during the
Iditarod 1049-mile dogsled race.
Cox C, Gaskill S, Ruby B, Uhlig S.
Department of Health and Human Performance, University of Montana, Missoula, MT
59812-4536, USA.
The purpose of the present case study was threefold: (a) to estimate intake and
expenditure of a dog driver (musher) while participating in the Iditarod, (b) to
determine the hydration status of the musher at the completion of the event, and
(c) to evaluate training related changes in aerobic capacity and body
composition of a long-distance dog sled driver in preparation for and following
completion of a 1049-mile (1692-km) sled dog race. Actual energy intake during
the Iditarod Sled Dog Race was estimated at 8,921 kilojoules (kJ) per day.
Nutrient intake expressed as percentage kJ of total energy (14%, 44% and 42% for
protein, carbohydrates, and fat, respectively). Weight loss of .72 kg of body
weight indicated an energy deficit of 1819 kJ per day during the race. Total
energy needs per day were calculated to be 10,740 kJ/day. An increase in
hematocrit and hemoglobin during the race may indicate dehydration during the
event. There was an improvement in aerobic fitness during on-snow training as
determined by ventilatory threshold and VO2peak data. Fat-free mass was
maintained during training (46.4 kg), with a concomitant decrease in fat (2.4
kg). Fat-free mass was also maintained during the 12-day race.
Publication Types:
Case Reports
PMID: 14669929 [PubMed]
97: J Exp Biol. 2004 Jan;207(Pt 2):307-18.
Seasonal metabolic depression, substrate utilisation and changes in scaling
patterns during the first year cycle of tegu lizards (Tupinambis merianae).
de Souza SC, de Carvalho JE, Abe AS, Bicudo JE, Bianconcini MS.
Departamento de Fisiologia, Instituto de Biociencias, Universidade de Sao Paulo,
05508-900 Sao Paulo, SP, Brazil. scrsouza@ib.usp.br
The tegus increase in body mass after hatching until early autumn, when the
energy intake becomes gradually reduced. Resting rates of oxygen consumption in
winter drop to 20% of the values in the active season ((O(2))=0.0636 ml g(-1)
h(-1)) and are nearly temperature insensitive over the range of 17-25 degrees C
(Q(10)=1.55). During dormancy, plasma glucose levels are 60% lower than those in
active animals, while total protein, total lipids and beta-hydroxybutyrate are
elevated by 24%, 43% and 113%, respectively. In addition, a significant
depletion of liver carbohydrate (50%) and of fat deposited in the visceral fat
bodies (24%) and in the tail (25%) and a slight loss of skeletal muscle protein
(14%) were measured halfway through the inactive period. Otherwise, glycogen
content is increased 4-fold in the brain and 2.3-fold in the heart of dormant
lizards, declining by the onset of arousal. During early arousal, the young
tegus are still anorexic, although (O(2)) is significantly greater than winter
rates. The fat deposits analysed are further reduced (62% and 45%, respectively)
and there is a large decrease in tail muscle protein (50%) together with a
significant increase in glycogen (2-3-fold) and an increase in plasma glucose
(40%), which suggests a role for gluconeogenesis as a supplementary energy
source in arousing animals. No change is detectable in citrate synthase
activity, but beta-hydroxyacyl CoA dehydrogenase activities are strongly
affected by season, reaching a 3-fold and 5-fold increase in the liver tissue of
winter and arousing animals, respectively, and becoming reduced by half in
skeletal muscle and heart of winter animals compared with late fall or spring
active individuals. From hatching to late autumn, the increase of the fat body
mass relatively to body mass is disproportionate (b=1.44), and the mass exponent
changes significantly to close to 1.0 during the fasting period. The concomitant
shift in the (O(2)) mass exponent in early autumn (b=0.75) to values
significantly greater than 1.0 in late autumn and during winter dormancy
indicates an allometric effect on the degree of metabolic depression related to
the size of the fat stores and suggests greater energy conservation in the
smaller young.
PMID: 14668314 [PubMed]
98: Br J Nutr. 2003 Nov;90(5):849-52.
Lipase inhibition attenuates the acute inhibitory effects of oral fat on food
intake in healthy subjects.
O'Donovan D, Feinle-Bisset C, Wishart J, Horowitz M.
Department of Medicine, University of Adelaide, Royal Adelaide Hospital, North
Terrace, South Australia 5000, Australia.
The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces
fat absorption by about 30%. However, the mean weight loss induced by orlistat
is less than expected for the degree of fat malabsorption. It was hypothesised
that lipase inhibition with orlistat attenuates the suppressive effects of oral
fat on subsequent energy intake in normal-weight subjects. Fourteen healthy,
lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied
twice, in a double-blind fashion. The subjects received a high-fat yoghurt
'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat
(120 mg) on one study day (and no orlistat on the other 'control' day), 30 min
before ad libitum access to food and drinks; energy intake was assessed during
the following 8 h. Blood samples were taken at regular intervals for the
measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal
fat collection following each study. Energy intake during the day was greater
following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ)
(P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma
CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM
0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no
difference in the area under the curve 0-510 min between the two study days. Fat
excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484
(SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute
inhibitory effect of fat on subsequent energy intake is attenuated by orlistat
and the increase in energy intake approximates the energy lost due to fat
malabsorption.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14667178 [PubMed]
99: Am J Physiol Endocrinol Metab. 2004 Jan;286(1):E57-63.
Endurance training partially reverses dietary-induced leptin resistance in
rodent skeletal muscle.
Steinberg GR, Smith AC, Wormald S, Malenfant P, Collier C, Dyck DJ.
Department of Human Biology and Nutritional Sciences, University of Guelph,
Guelph, Ontario, Canada N1G 2W1.
Leptin acutely stimulates skeletal muscle fatty acid (FA) metabolism in lean
rodents and humans. This stimulatory effect is eliminated following the feeding
of high-fat diets in rodents as well as in obese humans. The mechanism(s)
responsible for the development of skeletal muscle leptin resistance is unknown;
however, a role for increased suppressor of cytokine signaling-3 (SOCS3)
inhibition of the leptin receptor has been demonstrated in other rodent tissues.
Furthermore, whether exercise intervention is an effective strategy to prevent
or attenuate the development of skeletal muscle leptin resistance has not been
investigated. Toward this end, 48 Sprague-Dawley rats (175-190 g; approximately
2-3 mo of age) were fed control or high-fat (60% kcal) diets for 4 wk and either
remained sedentary or were treadmill trained. In control diet-fed animals that
remained sedentary (CS) or were endurance trained (CT), leptin stimulated FA
oxidation (CS +32 +/- 15%, CT +30 +/- 17%; P < 0.05), suppressed triacylglycerol
(TAG) esterification (CS -17 +/- 7%, CT -24 +/- 8%; P < 0.05), and reduced the
esterification-to-oxidation ratio (CS -19 +/- 13%, CT -29 +/- 10%; P < 0.001) in
soleus muscle. High-fat feeding induced leptin resistance in the soleus of
sedentary rats (FS), whereas endurance exercise training (FT) restored the
ability of leptin to suppress TAG esterification (-19 +/- 9%, P = 0.038).
Training did not completely restore the ability of leptin to stimulate FA
oxidation. High-fat diets stimulated SOCS3 mRNA expression irrespective of
training status (FS +451 +/- 120%, P = 0.024; FT +381 +/- 141%, P = 0.023). Thus
the development of skeletal muscle leptin resistance appears to involve an
increase in SOCS3 mRNA expression. Endurance training was generally effective in
preventing the development of leptin resistance, although this did not appear to
require a decrease in SOCS3 expression. Future studies should examine changes in
the actual protein content of SOCS3 in muscle and establish whether aerobic
exercise is also effective in treating leptin resistance in humans.
PMID: 14662513 [PubMed]
100: Arch Mal Coeur Vaiss. 2003 Sep;96 Spec No 6:7-12.
[Heart and nutrition: which fatty acids for which cardiac function?]
[Article in French]
Grynberg A.
INRA UR 1154, faculte de pharmacie, universite Paris-Sud, 5, rue Jean-Baptiste
Clement, 92296 Chatenay-Malabry. grynberg@jouy.inra.fr
Cardiovascular risk factors are often related to diet and the dietary fatty
acids play a leading role quantitatively and qualitatively. In addition to the
demonstration of the beneficial properties of n-3 PUFA on the development of
atherosclerosis, there is a growing body of experimental evidence on the
implication of n-3 PUFA in the regulation of cardiac function because of cardiac
enrichment with n-3 PUFA to the detriment of arachidonic acid. The
antiarrhythmic effect of these PUFA has been demonstrated in several animal
species, the positive results of the GISSI-prevenzione study being partially
associated with this property. This effect is related to the presence of DHA in
cardiac phospholipids but the molecular mechanism is poorly understood.
Moreover, the presence of DHA in the membranes decreases the production of cAMP
induced by a b-adrenergic stimulation. This characteristic related to the
interaction between the protein receptor complex and its environment provokes
effects similar to those of a betablocker specifically due to the presence of
DHA and not to the decrease in arachidonic acid. Finally, n-3 PUFA induce a
reduction of cardiac b-oxidation and oxygen consumption in the animal. This
effect, mild undr physiological conditions, manifests itself during
post-ischaemic reperfusions as an improvement of metabolic recovery and
ventricular function. In conclusion, the relationship between the heart and
fatty acids will change because of the increasing incidence of cardiac failure
associated with a chronic catabolic state. Daily dietary PUFA, in particular the
n-3 forms, is insufficient, especially when a hypertrophic heart has to increase
its membrane mass. In view of the positive effects of a high BMI on
morbi-mortality of cardiac failure, nutrition and cardiology may have to
reinforce their relationship in the short-term.
Publication Types:
Review
Review, Tutorial
PMID: 14655544 [PubMed]
101: Biochim Biophys Acta. 2003 Nov 30;1635(1):29-36.
Divergent effects of eicosapentaenoic and docosahexaenoic acid ethyl esters, and
fish oil on hepatic fatty acid oxidation in the rat.
Hong DD, Takahashi Y, Kushiro M, Ide T.
Division of Physiology and Nutrition, Laboratory of Nutritional Biochemistry,
National Food Research Institute, 2-1-12 Kannondai, Tsukuba 305-8642, Japan.
The physiological activity of fish oil, and ethyl esters of eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA) affecting hepatic fatty acid oxidation
was compared in rats. Five groups of rats were fed various experimental diets
for 15 days. A group fed a diet containing 9.4% palm oil almost devoid of n-3
fatty acids served as a control. The test diets contained 4% n-3 fatty acids
mainly as EPA and DHA in the form of triacylglycerol (9.4% fish oil) or ethyl
esters (diets containing 4% EPA ethyl ester, 4% DHA ethyl ester, and 1% EPA plus
3% DHA ethyl esters). The lipid content of diets containing EPA and DHA ethyl
esters was adjusted to 9.4% by adding palm oil. The fish oil diet and ethyl
ester diets, compared to the control diet containing 9.4% palm oil, increased
activity and mRNA levels of hepatic mitochondrial and peroxisomal fatty acid
oxidation enzymes, though not 3-hydroxyacyl-CoA dehydrogenase activity. The
extent of the increase was, however, much greater with the fish oil than with
EPA and DHA ethyl esters. EPA and DHA ethyl esters, compared to the control
diet, increased 3-hydroxyacyl-CoA dehydrogenase activity, but fish oil strongly
reduced it. It is apparent that EPA and DHA in the form of ethyl esters cannot
mimic the physiological activity of fish oil at least in affecting hepatic fatty
acid oxidation in rat.
PMID: 14642774 [PubMed]
102: Biochem Soc Trans. 2003 Dec;31(Pt 6):1270-3.
Modulation of carbohydrate and fat utilization by diet, exercise and
environment.
Jeukendrup AE.
Human Performance Laboratory, School of Sport and Exercise Sciences, University
of Birmingham, Edgbaston, Birmingham B15 2TT, U.K. a.e.jeukendrup@bham.ac.uk
At rest and during exercise carbohydrate and fat are the predominant substrates.
They are oxidized simultaneously but the relative contribution of these two
substrates is dependent on a variety of factors including the exercise intensity
and duration, diet, environmental conditions and training status. Changes in
carbohydrate metabolism during the transition from rest to exercise and from
low- to high-intensity exercise are mainly due to allosteric regulation. The
factors that up-regulate fat metabolism in the transition to moderate-intensity
exercise and the factors that result in a down-regulation of fat metabolism at
higher intensities are incompletely understood. Substrate use is further
modulated by the endocrine milieu (e.g. catecholamines, insulin, cortisol) and
possibly cytokines (e.g. interleukin-6). With increasing duration of exercise
there are marked increases in fat metabolism and decreases in carbohydrate
metabolism and this has been ascribed mainly to substrate availability. Both
acute food intake and chronic diets also have profound effects on substrate
utilization. An increase in carbohydrate intake will rapidly suppress fat
metabolism and increase carbohydrate metabolism whereas such an adaptation to a
high-fat diet may take several days. The environmental conditions can also alter
substrate use; high ambient temperatures can increase glycogen breakdown as a
result of increased body core temperature and increased circulation
catecholamines. Low temperatures can also increase carbohydrate metabolism,
especially when shivering. In addition to these factors adaptation to training,
in particular endurance training, will reduce the reliance on carbohydrate
metabolism and increase fat oxidation, especially from intramuscular
triacylglycerol stores.
PMID: 14641041 [PubMed]
103: Prev Med. 2003 Dec;37(6 Pt 2):S70-9.
The impact of the Pathways intervention on psychosocial variables related to
diet and physical activity in American Indian schoolchildren.
Stevens J, Story M, Ring K, Murray DM, Cornell CE, Juhaeri, Gittelsohn J.
Department of Nutrition, School of Public Health, University of North Carolina,
Chapel Hill, NC 27599-7400, USA. June_Stevens@unc.edu
BACKGROUND: The purpose of this study was to examine the impact of the Pathways
intervention on pychosocial variables related to physical activity and diet in
American Indian children. METHODS: Schools serving American Indian children were
randomized to a multicomponent intervention or control condition. At baseline
(fall of third grade) and in the spring semester of third, fourth, and fifth
grades 755 boys and 692 girls completed a classroom-administered questionnaire.
The questionnaire assessed self-efficacy, knowledge, and behavioral intentions
related to diet and physical activity, as well as weight loss behaviors and body
image. RESULTS: Knowledge of nutrition and physical activity messages increased
in both boys and girls in the intervention group compared to controls; however,
knowledge of which foods contained more fat did not increase consistently.
Compared to controls, self-efficacy to be physically active increased among
girls in intervention schools, but not among boys, whereas self-efficacy to make
more healthy food choices did not increase more than in controls in either
gender. In the intervention group, compared to controls, healthy food intentions
and participation in physically active behaviors increased in both boys and
girls. Perception of healthy body size and weight loss attempts did not differ
in the intervention and control groups. CONCLUSION: The Pathways intervention
program had a positive impact on several aspects of obesity-related knowledge,
attitudes, and behaviors.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14636811 [PubMed]
104: J Anim Physiol Anim Nutr (Berl). 2003 Dec;87(11-12):408-20.
Effect of dietary protein on lean body wasting in dogs: correlation between loss
of lean mass and markers of proteasome-dependent proteolysis.
Wakshlag JJ, Barr SC, Ordway GA, Kallfelz FA, Flaherty CE, Christensen BW,
Shepard LA, Nydam DV, Davenport GM.
Department of Clinical Sciences, Cornell University, College of Veterinary
Medicine, Ithaca, NY, USA. jw37@cornell.edu
To determine the effect of dietary protein intake on lean body wasting in adult
canines a study was undertaken to investigate the Ubiquitin Proteasome (UP)
pathway and concurrent changes in lean and fat body mass of canines fed variable
sources and concentrations of dietary protein. Purpose-bred, intact female
canines (56) between the ages of 2 and 3 years were fed either 12 or 28% protein
diet for 10 weeks. Each diet contained variable amounts of corn gluten meal and
chicken protein sources in ratios of 100 : 0, 67 : 33, 33 : 67 and 0 : 100 per
cent (w/w), respectively. All diets were isocaloric with calories coming from
protein : fat : carbohydrate at the respective ratios of 12 : 40 : 48% for the
12% diets, and 28 : 40 : 32% for the 28% diets. Standard dual energy X-ray
absorptiometry was performed to assess total body lean and fat mass at weeks 0
and 10 of the dietary trial. Muscle biopsies were also taken and processed for
protein determination and standard gel electrophoresis with subsequent Western
blotting for 20S proteasome and PA700 regulatory cap subunit p31. Statistical
analysis revealed a moderate degree of correlation between increasing quantities
of corn gluten, which is low in essential amino acids (i.e. lysine, tryptophan),
and increasing loss of lean body mass over the 10-week study (R = 0.56).
Furthermore, a moderate degree of correlation was observed between increasing
concentrations of corn gluten protein and decreased expression of the p31
subunit of the 26S proteasome (R = 0.49). Additionally, the dogs consuming the
12% protein diets had a significant increase in fat mass regardless of the
protein source. These findings suggest that lean body wasting in adult canines
can be associated with the consumption of low protein diets consisting of
predominantly corn gluten, which is likely due to imbalances or subclinical
deficiencies of specific essential amino acids, and that low protein diets may
augment accumulation of adipose tissue. Although the mechanisms remain unclear,
alteration of molecular targets of skeletal muscle proteolysis, specifically
involving the UP pathway occur.
PMID: 14633050 [PubMed]
105: Neuroimaging Clin N Am. 2003 Aug;13(3):465-83.
Nasopharynx: clinical, pathologic, and radiologic assessment.
Weber AL, al-Arayedh S, Rashid A.
Department of Radiology, Massachusetts Eye and Ear Infirmary, 243 Charles
Street, Boston, MA 02114, USA. alweber1@aol.com
NPC represents 0.2% of malignant disease in the white population but is more
common in southern China, among Chinese in East Asia and the United [figure: see
text] States, and in North Africa, including Saudi Arabia. NPC in these ethnic
groups tends to manifest at a younger age. Undifferentiated carcinoma is the
most common histopathologic type and is associated with EBV. The tumor is
optimally assessed with CT and MR imaging for staging; PET scanning provides
optimal assessment of recurrent tumor or small lymph node metastases. The
primary tumor in the nasopharynx may be small and infiltrating, causing no or
only a small mass effect in the nasopharynx. In these cases, obliteration of fat
planes and loss of muscle boundaries are important diagnostic findings, which
are best evaluated with MR imaging including, Gd-DTPA with fat suppression. The
size of the NPC varies from 1 to 2 cm to large tumors that extend to the
oropharynx, PPS, nasal cavities, paranasal sinuses, and orbits. Skull base
erosion is independent of the size of the nasopharyngeal tumor and ranges from
slight erosion to extensive destruction. A concomitant finding is intracranial
invasion, predominantly to the basal cisterns and cavernous sinuses associated
with cranial nerve palsies. Intracranial invasion should be assessed with
contrast MR imaging. Lymph node metastases in the neck are present in 90% of
cases and are bilateral in 50% of cases. In a small percentage of cases,
extension of lymph node metastases to the mediastinum and hilar areas are
encountered. Distant metastases involve the lungs, skeleton, and liver, and
occasionally the choroid. They are usually present at the initial presentation
[figure: see text] and increase in frequency in advanced disease and in
recurrent tumors. In addition, the metastatic lymph nodes in the neck reveal no
specific imaging features that would allow differentiation from other lymph node
metastases. They may be discrete, often multiple, and large and bulky displaying
a variable degree of necrosis and enhancement following introduction of contrast
material. Local recurrence manifests commonly within the first 2 to 3 years
posttherapy and is optimally evaluated by MR imaging and PET scanning.
Publication Types:
Review
Review, Academic
PMID: 14631685 [PubMed]
106: J Gerontol A Biol Sci Med Sci. 2003 Nov;58(11):1002-8.
Testosterone supplementation for aging-associated sarcopenia.
Bhasin S.
Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew
University, Los Angeles, California 90059, USA. sbhasin@ucla.edu
Aging of humans is associated with a loss of muscle mass and function, and an
increase in fat mass. Epidemiologic studies have demonstrated a correlation
between bioavailable testosterone concentrations and fat-free mass and muscle
strength. Testosterone replacement in older men with low testosterone levels
increases fat-free mass and muscle strength, and decreases fat mass. However, we
do not know whether testosterone replacement improves physical function and
other health-related outcomes, or reduces the risk of disability, falls, or
fractures in older men with low testosterone levels. The long-term risks and
benefits of testosterone supplementation in older men are not known.
Publication Types:
Review
Review, Tutorial
PMID: 14630881 [PubMed]
107: Int J Food Sci Nutr. 2004 Feb;55(1):27-35.
Time-course changes in macronutrient metabolism induced by a nutritionally
balanced low-calorie diet in obese women.
Labayen I, Diez N, Parra MD, Gonzalez A, Martinez JA.
Department of Physiology and Nutrition, C/Irunlarrea, University of Navarra,
31008 Pamplona, Spain.
The use of low-calorie diets is a common strategy for body-weight reduction
purposes, but the time-course of the metabolic changes induced by moderately
energy-restricted, otherwise balanced, diets is still poorly known. The aim of
this nutritional intervention design was to study in obese women the effect of a
balanced low-calorie diet on the metabolic rate, and metabolic fuel utilization
changes during the weight loss process through the application of breath tests
with stable isotope-labeled tracers. Seven obese (body mass index >30 kg/m(2))
women were assigned to a 10-week dietary hypoenergetic intervention regime
supplying 55% of energy as carbohydrate, 30% as fat and 15% as protein.
Metabolic rate and substrate utilization were evaluated for 6 h in separate
occasions during the weight loss program by indirect calorimetry and after
13C-labeled glucose, triolein and leucine administration. Body weight loss after
10 weeks was 4.2+/-1.1 kg, while the percent body fat decrease was about 5%.
Slimming was accompanied by a marked decrease in fasting leptin (about 25%).
Postprandial carbohydrate utilization after the administration of a test meal
with the same macronutrient distribution as the experimental low-energy diet was
decreased (24.1%, P<0.05) as a consequence of the dietary restriction, which was
associated with lower insulin plasma levels (P<0.05). Although protein and lipid
oxidation were not significantly different after weight reduction (day 1 versus
day 70), the metabolic utilization of these substrates tended to increase.
Moreover, marginally significant indications obtained on days 15 and 45 suggest
that the weight and body composition changes are attributable to a shift in
endogenous and exogenous glucose utilization in favor of lipid burning. The
breath tests determinations, which were performed on different occasions along
the experimental trial, confirmed that the cumulative 13C output decreased for
labeled tracers with time, being only statistically significant for the glucose
utilization between days 15 and 45. In summary, the weight and fat mass losses
were associated with a lower carbohydrate oxidation, which were probably
compensated by an increase in lipid oxidation without major changes in protein
mobilization.
PMID: 14630589 [PubMed]
108: Am J Physiol Endocrinol Metab. 2004 Mar;286(3):E354-62. Epub 2003 Nov 18.
Excess body fat in men decreases plasma fatty acid availability and oxidation
during endurance exercise.
Mittendorfer B, Fields DA, Klein S.
Center for Human Nutrition and Department of Internal Medicine, Washington
University School of Medicine, St. Louis, Missouri 63110, USA.
The effect of relative body fat mass on exercise-induced stimulation of
lipolysis and fatty acid oxidation was evaluated in 15 untrained men (5 lean, 5
overweight, and 5 obese with body mass indexes of 21 +/- 1, 27 +/- 1, and 34 +/-
1 kg/m2, respectively, and %body fat ranging from 12 to 32%). Palmitate and
glycerol kinetics and substrate oxidation were assessed during 90 min of cycling
at 50% peak aerobic capacity (VO2 peak) by use of stable isotope-labeled tracer
infusion and indirect calorimetry. An inverse relationship was found between
%body fat and exercise-induced increase in glycerol appearance rate relative to
fat mass (r2 = 0.74; P < 0.01). The increase in total fatty acid uptake during
exercise [(micromol/kg fat-free mass) x 90 min] was approximately 50% smaller in
obese (181 +/- 70; P < 0.05) and approximately 35% smaller in overweight (230
+/- 71; P < 0.05) than in lean (354 +/- 34) men. The percentage of total fatty
acid oxidation derived from systemic plasma fatty acids decreased with
increasing body fat, from 49 +/- 3% in lean to 39 +/- 4% in obese men (P <
0.05); conversely, the percentage of nonsystemic fatty acids, presumably derived
from intramuscular and possibly plasma triglycerides, increased with increasing
body fat (P < 0.05). We conclude that the lipolytic response to exercise
decreases with increasing adiposity. The blunted increase in lipolytic rate in
overweight and obese men compared with lean men limits the availability of
plasma fatty acids as a fuel during exercise. However, the rate of total fat
oxidation was similar in all groups because of a compensatory increase in the
oxidation of nonsystemic fatty acids.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 14625204 [PubMed]
109: Metabolism. 2003 Nov;52(11):1478-83.
The effect of combining plant sterols, soy protein, viscous fibers, and almonds
in treating hypercholesterolemia.
Jenkins DJ, Kendall CW, Marchie A, Faulkner D, Vidgen E, Lapsley KG, Trautwein
EA, Parker TL, Josse RG, Leiter LA, Connelly PW.
Clinical Nutrition and Risk Factor Modification Center, St. Michael's Hospital,
Toronto, Ontario, Canada.
Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets
containing almonds, or diets that are either low in saturated fat or high in
viscous fibers, soy proteins, or plant sterols. We have therefore combined all
of these interventions in a single diet (portfolio diet) to determine whether
cholesterol reductions could be achieved of similar magnitude to those reported
in recent statin trials which reduced cardiovascular events. Twenty-five
hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in
saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2
g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000
kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and
low-fat dairy foods. Fasting blood, blood pressure, and body weight were
obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4%
(P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio
diet, which also reduced the ratio of LDL-C to high-density
lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The
reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the
portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean
weight loss was similar on test and control diets (1.0 kg and 0.9 kg,
respectively). No difference was seen in blood pressure, HDL-C, serum
triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between
diets. Combining a number of foods and food components in a single dietary
portfolio may lower LDL-C similarly to statins and so increase the potential
effectiveness of dietary therapy.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14624410 [PubMed]
110: Metabolism. 2003 Nov;52(11):1413-7.
Effect of a one-year combined exercise training program on body composition in
men with coronary artery disease.
Santa-Clara H, Fernhall B, Baptista F, Mendes M, Bettencourt Sardinha L.
Exercise and Health Department, Faculty of Human Movement-Technical University
of Lisbon, Portugal. santaclar@tmh.utl.pt
Increased fat mass, particularly abdominal fat mass, is associated with poor
metabolic profiles and an increase in cardiovascular risk factors. The purpose
of this study was to evaluate the effect of a 1-year combined aerobic and
strength training regimen, compared to aerobic training only, on body
composition in patients with coronary artery disease (CAD). Thirty-six males
with CAD were assigned to 3 groups: 13 to weight training plus aerobic training
(combined training group [CT]), 13 to aerobic training only (aerobic training
group [AT]), and 10 to a control group (no exercise [CG]). Body composition was
determined by dual-energy x-ray absorptiometry (DEXA). Differences were observed
between groups at the end of the study, controlling for prevalues. The total and
trunk percent fat mass (%FM) were lower in CT compared with AT and CG (P<.05).
The total %FM in AT was significantly (P<.05) lower than in CG, but the %FM of
the trunk did not differ between the 2 groups. Fat-free mass (FFM) was
significantly higher in CT than in AT and CG (P<.05). The results suggest that a
long-term CT program is more effective than an AT program alone in producing
changes in body composition. The percentage changes in total and trunk fat mass
were higher in CT (-11% and -12%, respectively) than in AT (-2.4% and -0.7%,
respectively). Future studies need to investigate the specific health effects of
trunkal fat mass loss in patients with CAD.
Publication Types:
Clinical Trial
PMID: 14624399 [PubMed]
111: J Biol Chem. 2004 Feb 6;279(6):4051-7. Epub 2003 Nov 13.
Acylation-stimulating protein (ASP)/complement C3adesArg deficiency results in
increased energy expenditure in mice.
Xia Z, Stanhope KL, Digitale E, Simion OM, Chen L, Havel P, Cianflone K.
Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health
Centre, Montreal H3A 1A1, Canada.
Acylation-stimulating protein (ASP) acts as a paracrine signal to increase
triglyceride synthesis in adipocytes. In mice, C3 (the precursor to ASP)
knock-out (KO) results in ASP deficiency and leads to reduced body fat and
leptin levels yet they are hyperphagic. In the present study, we investigated
the mechanism for this energy repartitioning. Compared with wild-type (WT) mice,
male and female C3(-/-) ASP-deficient mice had elevated oxygen consumption (VO2)
in both the active (dark) and resting (light) phases of the diurnal cycle: +8.9%
males (p < 0.05) +9.4% females (p < 0.05). Increased physical activity
(movement) was observed during the dark phase in female but not in male KO
animals. Female WT mice moved 16.9 +/- 2.4 m whereas KO mice moved 30.1 +/- 5.4
m, over 12 h, +78.4%, p < 0.05). In contrast, there was no difference in
physical activity in male mice, but a repartitioning of dietary fat following
intragastric fat administration was noted. This was reflected by increased fatty
acid oxidation in liver and muscle in KO mice, with increased UCP2 (inguinal
fat) and UCP3 (muscle) mRNA expression (p = 0.005 and 0.036, respectively).
Fatty acid uptake into brown adipose tissue (BAT) and white adipose tissue (WAT)
was reduced as reflected by a decrease in the fatty acid incorporation into
lipids (BAT -68%, WAT -29%. The decrease of FA incorporation was normalized by
intraperitoneal administration of ASP at the time of oral fat administration.
These results suggest that ASP deficiency results in energy repartitioning
through different mechanisms in male and female mice.
PMID: 14615480 [PubMed]
112: Exp Biol Med (Maywood). 2003 Nov;228(10):1245-9.
Clinical implications of thermal therapy in lifestyle-related diseases.
Biro S, Masuda A, Kihara T, Tei C.
Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate
School of Medicine, Kagoshima University, Kagoshima 890-8520, Japan.
Systemic thermal therapy, such as taking a warm-water bath and sauna, induces
systemic vasodilation. It was found that repeated sauna therapy (60 degrees C
for 15 min) improved hemodynamic parameters, clinical symptoms, cardiac
function, and vascular endothelial function in patients with congestive heart
failure. Vascular endothelial function is impaired in subjects with
lifestyle-related diseases, such as hypertension, hyperlipidemia, diabetes
mellitus, obesity, and smoking. Sauna therapy also improved endothelial
dysfunction in these subjects, suggesting a preventive role for atherosclerosis.
In animal experiments, sauna therapy increases mRNA and protein levels of
endothelial nitric oxide synthase (eNOS) in aortas. In normal-weight patients
with appetite loss, repeated sauna therapy increased plasma ghrelin
concentrations and daily caloric intake and improved feeding behavior. In obese
patients, the body weight and body fat significantly decreased after 2 weeks of
sauna therapy without increase of plasma ghrelin concentrations. On the basis of
these data, sauna therapy may be a promising therapy for patients with
lifestyle-related diseases.
Publication Types:
Review
Review Literature
PMID: 14610268 [PubMed]
113: Holist Nurs Pract. 2003 Sep-Oct;17(5):250-61.
Attaining successful weight loss with an ideal macronutrient balance.
Kris-Etherton P, Champagne C, McManus K.
Department of Nutritional Sciences, The Pennsylvania State University,
University Park, Pa 16802, USA. penny_krisetherton@adelphia.net
A dramatic increase in the number of people who are overweight or obese in this
country presents a growing public health problem. Successful weight loss
requires diet, physical activity, and behavior modification interventions.
Weight loss diets with distinctively different macronutrient profiles have
resulted in short-term weight loss. There is great interest in identifying the
most effective strategies to achieve long-term weight loss. Individualizing
weight loss interventions, including diet, will be important to facilitate
significant weight loss on a population basis. Nurses and nurse practitioners
can play an integral role in supporting their patient's weight loss efforts.
PMID: 14596375 [PubMed]
114: Endocrinology. 2004 Feb;145(2):487-94. Epub 2003 Oct 30.
Comment in:
Endocrinology. 2004 Feb;145(2):484-6.
Adiponectin ameliorates dyslipidemia induced by the human immunodeficiency virus
protease inhibitor ritonavir in mice.
Xu A, Yin S, Wong L, Chan KW, Lam KS.
Department of Medicine, The University of Hong Kong, L8-33A, New Laboratory
Block, 21 Sassoon Road, Hong Kong, China. amxu@hkucc.hku.hk
Although the clinical application of HIV protease inhibitors (PIs) has markedly
reduced HIV-related morbidity and mortality, it is now recognized that PI-based
therapy often causes serious metabolic disorders, including hyperlipidemia and
premature atherosclerosis. The etiology of these adverse effects remains
obscure. Here, we demonstrate that deficiency of the fat-derived hormone
adiponectin might play a role. The steady-state mRNA levels of the adiponectin
gene and secretion of this protein from 3T3-L1 adipocytes are significantly
decreased after treatment with several PIs (indinavir, nelfinavir, and
ritonavir), with ritonavir having the greatest effect. Intragastric
administration of ritonavir into mice decreases plasma concentrations of
adiponectin and concurrently increases the plasma levels of triglyceride, free
fatty acids, and cholesterol. Adiponectin replacement therapy markedly
ameliorates ritonavir-induced elevations of triglyceride and free fatty acids.
These beneficial effects of adiponectin are partly due to its ability to
decrease ritonavir-induced synthesis of fatty acids and triglyceride, and to
increase fatty acid combustion in the liver tissue. In contrast, adiponectin has
little effect on ritonavir-induced hypercholesterolemia and hepatic cholesterol
synthesis. These results suggest that hypoadiponectinemia is partly responsible
for the metabolic disorders induced by HIV PIs, and adiponectin or its agonists
might be useful for the treatment of these disorders.
PMID: 14592951 [PubMed]
115: Med Hypotheses. 2003 Nov-Dec;61(5-6):535-42.
PTH excess may promote weight gain by impeding catecholamine-induced
lipolysis-implications for the impact of calcium, vitamin D, and alcohol on body
weight.
McCarty MF, Thomas CA.
Pantox Laboratories, San Diego, CA 92109, USA. mccarty@pantox.com
Increased free intracellular calcium ([Ca(2+)](i)) in adipocytes blunts the
lipolytic response to catecholamines by activating phosphodiesterase 3B - the
same enzyme that mediates the antilipolytic effect of insulin - while also
compromising the efficiency of insulin-stimulated glucose uptake. Physiological
increases in parathyroid hormone (PTH) have been shown to increase [Ca(2+)](i)
in adipocytes. These considerations may rationalize recent evidence that high
dietary intakes of calcium and/or dairy products may reduce risk for obesity,
diabetes, and insulin-resistance syndrome, and they predict that other dietary
measures which down-regulate PTH - such as good vitamin D status, and moderation
in phosphate and salt intakes - may likewise be beneficial in these respects.
Consistent with this position are reports that body weight is elevated in
elderly subjects with both primary and secondary hyperparathyroidism;
furthermore, insulin resistance is a well-known complication of both forms of
hyperparathyroidism. The fact that regular alcohol consumption is associated
with decreased PTH secretion may help to explain why moderate drinkers are less
prone to insulin resistance, diabetes, and - in women - obesity. Down-regulation
of PTH cannot be expected to promote dramatic weight loss, but in the long-term
it may lessen risk for significant weight gain and diabetes, and conceivably may
potentiate the fat loss achievable with caloric restriction and/or exercise.
PMID: 14592784 [PubMed]
116: Eur J Endocrinol. 2003 Nov;149(5):421-4.
Absence of exercise-induced variations in adiponectin levels despite decreased
abdominal adiposity and improved insulin sensitivity in type 2 diabetic men.
Boudou P, Sobngwi E, Mauvais-Jarvis F, Vexiau P, Gautier JF.
Department of Hormonal Biology, Saint-Louis University Hospital, Assistance
Publique Hospitaux de Paris, Paris, France. philippe.boudou@sls.ap-hop-paris.fr
OBJECTIVE: We investigated the effect of an intensive training program on
fasting leptin and adiponectin levels. METHODS: Sixteen middle-aged men with
type 2 diabetes were randomly assigned to either a training or control group.
The training program consisted of 8 weeks of supervised endurance exercise (75%
VO(2peak), 45 min) twice a week, with intermittent exercise (five 2 min
exercises at 85% VO(2peak) separated by 3 min exercises at 50% VO(2peak)) once a
week, on an ergocycle. RESULTS: Training decreased abdominal fat by 44%,
increased mid-thigh muscle cross-sectional area by 24%, and improved insulin
sensitivity by 58% without significant change in body weight. Compared with
controls, no significant variation in leptin or adiponectin levels was observed.
However, in the trained group, change in adiponectin correlated with change in
body weight (Spearman rank correlation, r(s):-0.76, P=0.03) but not with insulin
sensitivity or abdominal adiposity variations. CONCLUSIONS: An 8 week intensive
training program inducing a marked reduction in abdominal fat and increase in
insulin sensitivity does not affect adiponectin and leptin levels in men with
type 2 diabetes.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14585088 [PubMed]
117: Drug Saf. 2003;26(14):1027-48.
A benefit-risk assessment of sibutramine in the management of obesity.
Nisoli E, Carruba MO.
Center for Study and Research on Obesity, Department of Preclinical Sciences,
University of Milan, LITA Vialba, Luigi Sacco Hospital, Milan, Italy.
enzo.nisoli@unimi.it
Obesity is a multifactorial, chronic disorder that has reached epidemic
proportions in most industrialised countries and is threatening to become a
global epidemic. Clinical management of obese patients is complex and serious
doubts have arisen with regard to safety and efficacy of drug therapy. Following
the withdrawal of fenfluramine and dexfenfluramine in 1997, interest has focused
on novel anti-obesity drugs. Pharmacological approaches to the management of
obesity can, in broad terms, use different distinct strategies: firstly, to
reduce energy intake; secondly, to increase energy expenditure; and thirdly, to
alter the partitioning of nutrients between fat and lean tissue. Sibutramine is
a serotonin-noradrenaline (norepinephrine) reuptake inhibitor indicated for the
management of obesity in conjunction with a reduced calorie diet. The
pharmacological mechanisms by which sibutramine exerts its weight loss effect
are likely due to a combination of reduced appetite, feelings of satiety and
possibly the induction of thermogenesis. The efficacy of sibutramine for
inducing initial weight loss and the subsequent maintenance of weight loss is
well proven in short- and long-term clinical trials of up to 2 years' duration.
Most individual placebo-controlled trials and pooled estimates found that the
drug produced statistically significant greater weight loss than placebo at all
observed endpoints (weighted mean difference for weight change at 8 weeks: -3.4
kg; mean difference range for weight change at 6 months: -4.0 to -9.1 kg; and at
1 year: -4.1 to -4.8 kg). The most frequent dosage regimen in these trials was
10-20 mg daily. Findings suggested a dose-effect relationship in terms of weight
loss. Sibutramine was also associated with better weight maintenance relative to
placebo (statistically significant difference). Results from mainly small trials
showed that sibutramine produced more favourable outcomes in terms of loss of
fat mass, reduction in body mass index and loss of > or = 5-10% of initial
bodyweight. The most commonly reported adverse effects of sibutramine are
headache, constipation and nausea. Certain adverse events associated with the
nervous system, including dizziness, dry mouth and insomnia, are reported by >
5% of patients receiving sibutramine. Increases in blood pressure and heart rate
were possible adverse effects that require regular monitoring especially in
obese hypertensive patients. Neither left-sided cardiac valve disease nor
primary pulmonary hypertension was associated with the use of sibutramine. The
assessment of the benefit-risk profile of sibutramine remained positive,
although the product must be kept under regular review.
Publication Types:
Review
Review, Tutorial
PMID: 14583064 [PubMed]
118: Diabetes Care. 2003 Nov;26(11):3148-52.
Effects of pioglitazone versus diet and exercise on metabolic health and fat
distribution in upper body obesity.
Shadid S, Jensen MD.
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
OBJECTIVE: Insulin resistance is associated with visceral adiposity, and
interventions that reduce this depot, e.g., diet and exercise, improve insulin
resistance. Thiazolidinediones (TZDs) also improve insulin action but
paradoxically increase total fat mass, perhaps through remodeling (recruitment
of smaller fat cells) and redistribution of adipose tissue. We assessed the
effects of pioglitazone versus diet and exercise on fat distribution and the
relationship between fat distribution and insulin sensitivity in upper body
obesity. RESEARCH DESIGN AND METHODS: Thirty-nine upper body obese,
insulin-resistant, nondiabetic men and premenopausal women were randomly
assigned to receive either 30 mg/day pioglitazone or a diet and exercise program
for 20 weeks. Before and after the intervention, insulin sensitivity, body
composition, body fat distribution (waist-to-hip ratio [WHR], computed
tomography abdomen, and dual-energy X-ray absorptiometry), and abdominal and
femoral fat cell size were assessed. RESULTS: Diet and exercise resulted in an
11.8 +/- 1.1 kg weight loss. Both diet and exercise and pioglitazone improved
insulin sensitivity, but only the former was associated with loss of
intra-abdominal fat. Pioglitazone increased total body fat, which preferentially
accumulated in the lower body depot in both men and women. WHRs decreased in
both groups. Abdominal fat cell size decreased (P = 0.06) after diet and
exercise. No statistically significant changes in fat cell size were observed in
pioglitazone-treated volunteers. CONCLUSIONS: In nondiabetic upper body obese
subjects, increasing insulin sensitivity via diet and exercise accompanies
reductions in visceral fat. Pioglitazone treatment also improves insulin
sensitivity and lowers WHR, but this is due to a selective increase in lower
body fat. This confirms a site-specific responsiveness of adipose tissue to TZD
and suggests that improvements in insulin sensitivity by pioglitazone are
achieved independent of changes in intra-abdominal fat.
PMID: 14578253 [PubMed]
119: Eur J Clin Nutr. 2003 Nov;57(11):1386-93.
Lifestyle factors associated with glycaemic control and body mass index in older
adults with diabetes.
Grylls WK, McKenzie JE, Horwath CC, Mann JI.
Paraparaumu Hospital, Capital and Coast Health, Private Bag, Wellington, New
Zealand. grylls@compuserve.com
OBJECTIVE: To investigate the relations between lifestyle factors (diet and
exercise), glycated haemoglobin (HbA(1c)) and body mass index (BMI) in older
adults with diabetes. DESIGN AND SETTING: A community hospital-based
cross-sectional study of 150 noninstitutionalized, ambulatory adults (>/=65 y)
with diabetes, residing within New Zealand's Kapiti region. SUBJECTS: Patients
were recruited from all general practices; two diabetes clinics; local diabetes
society and through advertisements in community newspapers. A total of 211
eligible people were identified, but 60 refused to participate and one withdrew.
In all, 150 people completed the study (71% participation rate). METHODS:
Nutrient intakes were calculated by a food-frequency questionnaire. Physical
activity was assessed by interview using a validated questionnaire. Medical
history and demographic data were obtained by interview or self-completed
questionnaires; height, weight and HbA(1c) were measured. Multivariate models
using bootstrapping and stepwise linear regression were used to select factors
associated with HbA(1c) and BMI. RESULTS: Each five-unit increase in energy from
dietary saturated fat and five-unit increase in BMI were associated with 6% (95%
confidence interval=2-10%; P=0.004) and 4% (0.3-7%; P=0.031) increases in
HbA(1c), respectively. For females with moderate, compared with low overall
activity, there was a 14% (7-20%; P=0.000) reduction in BMI while for males the
reduction was only 5% (-1-11%; P=0.116). BMI decreased 5% (2-9%; P=0.004) with
each 10-y increase in age, while a five-unit increment in energy from dietary
sucrose was associated with a 6% (1-11%; P=0.025) increase in BMI. CONCLUSIONS:
Reducing dietary saturated fat and excess body weight may be useful means of
improving glycaemic control in older adults with diabetes. Increasing physical
activity and reducing energy from dietary sucrose may assist weight control, the
former particularly in women.
PMID: 14576751 [PubMed]
120: Antimicrob Agents Chemother. 2003 Nov;47(11):3384-92.
Mitochondrial and metabolic effects of nucleoside reverse transcriptase
inhibitors (NRTIs) in mice receiving one of five single- and three dual-NRTI
treatments.
Note R, Maisonneuve C, Letteron P, Peytavin G, Djouadi F, Igoudjil A, Guimont
MC, Biour M, Pessayre D, Fromenty B.
INSERM Unite 481 and Centre Claude Bernard de Recherches sur les Hepatites
Virales, Clichy, France.
Although treatments with nucleoside reverse transcriptase inhibitors (NRTIs) can
modify fat metabolism and fat distribution in humans, the mechanisms of these
modifications and the roles of diverse NRTIs are unknown. We studied the
mitochondrial and metabolic effects of stavudine (d4T), zidovudine (AZT),
didanosine (ddI), lamivudine (3TC), zalcitabine (ddC), and three combinations
(AZT-3TC, d4T-3TC, and d4T-ddI) in mice treated for 2 weeks with daily doses
equivalent to the human dose per body area. Concentrations of AZT and d4T in
plasma were lower when these drugs were administered with 3TC or ddI. Whatever
the treatment, mitochondrial DNA was not significantly decreased in muscle,
heart, brain, or white adipose tissue but was moderately decreased in liver
tissue after the administration of AZT, 3TC, or d4T alone. Blood lactate was
unchanged, even when NRTIs were administered at supratherapeutic doses. In
contrast, the level of plasma ketone bodies increased with the administration of
AZT or high doses of d4T but not with ddC, 3TC, or ddI, suggesting that the
thymine moiety could be involved. Indeed, the levels of plasma ketone bodies
increased in mice treated with beta-aminoisobutyric acid, a thymine catabolite.
Treatment with AZT, d4T, or beta-aminoisobutyric acid increased hepatic
carnitine palmitoyltransferase I (CPT-I) mRNA expression and the mitochondrial
generation of ketone bodies from palmitate. In conclusion, therapeutic doses of
NRTIs have no or moderate effects on mitochondrial DNA and no effects on plasma
lactate in mice. However, AZT and high doses of d4T increase the levels of
hepatic CPT-I, mitochondrial fatty acid beta-oxidation, and ketone bodies, and
these catabolic effects are reproduced by beta-aminoisobutyric acid, a thymine
metabolite.
PMID: 14576092 [PubMed]
121: Int J Obes Relat Metab Disord. 2003 Nov;27(11):1325-31.
Serum bFGF levels are reduced in Japanese overweight men and restored by a
6-month exercise education.
Seida A, Wada J, Kunitomi M, Tsuchiyama Y, Miyatake N, Fujii M, Kira S,
Takahashi K, Shikata K, Makino H.
Department of Medicine and Clinical Science, Okayama University Graduate School
of Medicine and Dentistry, Shikata-cho, Okayama, Japan.
OBJECTIVE: To investigate whether the changes in vascular endothelial growth
factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before
and after weight reduction in Japanese overweight men are associated with
changes in body mass index (BMI), visceral, subcutaneous fat, VO(2) and work
rate (WR) at ventilatory threshold (VT). DESIGN: Cross-sectional and
longitudinal clinical intervention study with exercise education. SUBJECTS: In
total, 30 Japanese overweight men (BMI, 29.0+/-2.2 kg/m(2)) and 31 normal-weight
men (BMI, 22.5+/-1.6 kg/m(2)) at baseline were enrolled: 30 overweight men (BMI,
29.0+/-2.2 kg/m(2)) were further enrolled into a 6-month exercise program.
MEASUREMENTS: Fat distribution evaluated by visceral fat (V) and subcutaneous
fat (S) areas measured with computed tomography scanning at umbilical levels,
angiogenic peptides including VEGF and bFGF, exercise tests at baseline and
after 6 months. RESULTS: In normal-weight and overweight subjects at baseline,
VEGF positively correlated with S area (r=0.350, P=0.007) but not with V area.
In contrast, bFGF negatively correlated with BMI (r=-0.619, P<0.001), S
(r=-0.457, P<0.001) and V areas (r=-0.466, P<0.001). By intervention with
exercise education, 30 overweight subjects showed reduction in BMI (29.0+/-2.2
to 28.0+/-2.0, P<0.001), V and S areas, increase in VO(2) and WR at VT, increase
in bFGF (9.21+/-5.82-21.2+/-7.04 ng/ml, P<0.001), and no change in VEGF
(1.45+/-0.72-1.88+/-0.52 ng/ml, P=0.016). The stepwise multiple regression
analysis revealed that DeltaBMI (beta=-6.052) and DeltaVO(2) (beta=2.806) were
independently related to DeltabFGF (P<0.001) and all other variables including
DeltaS area, and DeltaV area, and DeltaWR did not enter the equation at
significant levels. CONCLUSION: The present study indicated a negative
correlation between serum bFGF levels and BMI at baseline as well as an
association of DeltaBMI and DeltaVO(2) with DeltabFGF after exercise
intervention. The exercise-induced elevation of bFGF may be beneficial in the
prevention of the atherosclerosis in overweight subjects.
PMID: 14574342 [PubMed]
122: Physiol Behav. 2003 Oct;80(1):75-9.
A nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester,
attenuates lipoprivic feeding in mice.
Czech DA, Kazel MR, Harris J.
Biopsychology Laboratory, Department of Psychology, Marquette University,
SC-454, P.O. Box 1881, Milwaukee, WI 53201-1881, USA. donald.czech@marquette.edu
Possible involvement of nitric oxide (NO) in lipoprivic feeding was investigated
in nondeprived male ICR mice adapted to a high-fat diet in a within-subjects
design. Lipoprivation was induced by blocking fatty acid oxidation with
Na-mercaptoacetate (MA), which produces a short-term increase in feeding in mice
and rats. Food intake, measured at 1, 2, and 4 h following injection of 70 mg/kg
of MA, was attenuated in a dose related manner with increasing pretreatment dose
(1,10, 25 and 50 mg/kg sc) of the NO-synthase (NOS) inhibitor,
N(G)-nitro-L-arginine methyl ester (L-NAME), reaching statistical significance
at 10 mg/kg of L-NAME at h1 when compared to vehicle control condition. The
inactive isomer, D-NAME, was ineffective, thereby supporting stereospecific drug
action and directly implicating NO. A control experiment measured general
locomotor activity (grid crossings and rears) in an open arena under 10-50 mg/kg
of L-NAME in the same mice; both measures were significantly different from
vehicle condition only at the highest dose. These findings support involvement
of NO in lipoprivic hyperphagia; they are consistent with and extend research
linking NO and ingestive behaviors through use of NOS inhibitors. Possible
influences of confounds were discussed.
PMID: 14568310 [PubMed]
123: Prim Care. 2003 Jun;30(2):317-25.
The menopause and obesity.
Lovejoy JC.
Women's Nutrition Research Program, Pennington Biomedical Research Center,
Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
lovejoj@pbrc.edu
In summary, menopause tends to be associated with an increased risk of obesity
and a shift to an abdominal fat distribution with associated increase in health
risks. Changes in body composition at menopause may be caused by the decrease in
circulating estrogen, and, for fat distribution shifts, the relative increase in
the androgen-estrogen ratio is likely to be important. Clinicians need to be
aware of the likelihood of weight gain during the perimenopausal and
postmenopausal years because behavioral strategies for weight loss can be
effectively used in this population. Weight loss or prevention of weight gain is
likely to have significant health benefits for older women.
Publication Types:
Review
Review, Tutorial
PMID: 14567150 [PubMed]
124: Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):98-105. Epub 2003 Oct 16.
Comment in:
Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):4-6.
Genetic ablation of caveolin-1 confers protection against atherosclerosis.
Frank PG, Lee H, Park DS, Tandon NN, Scherer PE, Lisanti MP.
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300
Morris Park Ave, Golding 202, Bronx, NY 10461, USA.
OBJECTIVE: The development of atherosclerosis is a process characterized by the
accumulation of lipids in the form of modified lipoproteins in the
subendothelial space. This initiating step is followed by the subsequent
recruitment and proliferation of other cell types, including
monocytes/macrophages and smooth muscle cells. Here, we evaluate the potential
role of caveolae membrane domains in the pathogenesis of atherosclerosis by
using apolipoprotein E-deficient (ApoE-/-) mice as a model system. METHODS AND
RESULTS: Caveolin-1 (Cav-1) is a principal structural protein component of
caveolae membrane domains. To directly assess the in vivo role of caveolae and
Cav-1 in atherosclerosis, we interbred Cav-1-/- mice with ApoE-/- mice.
Interestingly, loss of Cav-1 resulted in a dramatic >2-fold increase in non-HDL
plasma cholesterol levels in the ApoE-/- background. However, despite this
hypercholesterolemia, we found that loss of Cav-1 gene expression was clearly
protective against the development of aortic atheromas, with up to an
approximately 70% reduction in atherosclerotic lesion area. Mechanistically, we
demonstrated that loss of Cav-1 resulted in the dramatic downregulation of
certain proatherogenic molecules, namely, CD36 and vascular cell adhesion
molecule-1. CONCLUSIONS: Taken together, our results indicate that loss of Cav-1
can counteract the detrimental effects of atherogenic lipoproteins. Thus, Cav-1
is a novel target for drug development in the pharmacologic prevention of
atheroma formation. Our current data also provide the first molecular genetic
evidence to support the hypothesis that caveolar transcytosis of modified
lipoproteins (from the blood to the sub-endothelial space) is a critical
initiating step in atherosclerosis.
PMID: 14563650 [PubMed]
125: Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E217-25. Epub 2003 Oct 14.
High-fat diet elevates resting intramuscular triglyceride concentration and
whole body lipolysis during exercise.
Zderic TW, Davidson CJ, Schenk S, Byerley LO, Coyle EF.
Department of Kinesiology and Health Education, The University of Texas at
Austin, Austin, Texas 78712, USA.
This study determined the role of intramuscular triglyceride (IMTG) and adipose
lipolysis in the elevated fat oxidation during exercise caused by a high-fat
diet. In four separate trials, six endurance-trained cyclists exercised at 50%
peak O2 consumption for 1 h after a two-day control diet (22% fat, CON) or an
isocaloric high-fat diet (60% fat, HF) with or without the ingestion of
acipimox, an adipose lipolysis inhibitor, before exercise. During exercise, HF
elevated fat oxidation by 72% and whole body lipolysis [i.e., the appearance
rate of glycerol in plasma (Ra glycerol)] by 79% compared with CON (P < 0.05),
and this was associated with a 36% increase (P < 0.05) in preexercise IMTG
concentration. Although acipimox lowered plasma free fatty acid (FFA)
availability, HF still increased fat oxidation and Ra glycerol to the same
magnitude above control as the increase caused by HF without acipimox (i.e.,
both increased fat oxidation 13-14 micromol.kg(-1).min(-1)). In conclusion, the
marked increase in fat oxidation after a HF diet is associated with elevated
IMTG concentration and whole body lipolysis and does not require increased
adipose tissue lipolysis and plasma FFA concentration during exercise. This
suggests that altered substrate storage in skeletal muscle is responsible for
increased fat oxidation during exercise after 2 days of an HF diet.
PMID: 14559721 [PubMed]
126: Maturitas. 2003 Oct 20;46(2):133-8.
Precedence of bone loss over changes in body composition and body fat
distribution within a few years after menopause.
Douchi T, Kosha S, Uto H, Oki T, Nakae M, Yoshimitsu N, Nagata Y.
Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima
University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
tomy@m3.kufm.kagoshima-u.ac.jp
OBJECTIVE: The present study investigated the sequence of certain phenomena with
a few years after menopause: bone mineral loss, decrease in lean body mass,
increase in body fat mass, or the shift toward upper body fat distribution.
METHODS: Subjects were 64 postmenopausal women aged 50-53 years with right side
dominance (mean age+/-S.D., 51.4+/-1.1 years), and 59 age-matched regularly
menstruating premenopausal women (51.7+/-1.2 years) serving as controls. Height,
weight, body mass index (BMI, wt./ht.(2)), age at menopause (in postmenopausal
women), and years since menopause (YSM) were recorded. Anthropometries, bone
mineral density (BMD), and body fat distribution were assessed by dual-energy
X-ray absorptiometry. RESULTS: Age at menopause and YSM in postmenopausal women
were 51.7+/-1.2 and 2.3+/-1.7 years, respectively. Age, height, weight, BMI did
not differ between the two groups. BMD of the bilateral arm, lumbar spine
(L2-4), pelvis, and total body were significantly lower in postmenopausal women.
However, leg BMD, trunk-leg fat ratio, body fat mass, and the lean body mass did
not differ between the two groups. CONCLUSION: Within a few years after
menopause, bone mineral loss precedes lean mass loss, increase in body fat mass,
and a shift toward upper body fat distribution. We can say that bone tissue is
more sensitive to hypogonadism than lean and fat tissues are.
PMID: 14559384 [PubMed]
127: J Theor Biol. 2003 Nov 7;225(1):33-44.
Decreased energy levels can cause and sustain obesity.
Wlodek D, Gonzales M.
National Center for Genome Resources, 2935 Rodeo Park Drive East, Santa Fe, NM
87508, USA. dkw@ncgr.org
Obesity has reached epidemic proportions and has become one of the major health
problems in developed countries. Current theories consider obesity a result of
overeating and sedentary life style and most efforts to treat or prevent weight
gain concentrate on exercise and food intake. This approach does not improve the
situation as may be seen from the steep increase in the prevalence of obesity.
This encouraged us to reanalyse existing information and look for biochemical
basis of obesity. Our approach was to ignore current theories and concentrate on
experimental data which are described in scientific journals and are available
from several databases. We developed and applied a Knowledge Discovery in
Databases procedure to analyse metabolic data. We began with the contradictory
information: in obesity, more calories are consumed than used up, suggesting
that obese people should have excess energy. On the other side, obese people
experience fatigue and decreased physical endurance that indicates diminished
energy supply in the body. The result of our work is a chain of metabolic events
leading to obesity. The crucial event is the inhibition of the TCA cycle at the
step of aconitase. It disturbs energy metabolism and results in ATP deficiency
with simultaneous fat accumulation. Further steps in obesity development are the
consequences of diminished energy supply: inhibition of beta-oxidation, leptin
resistance, increase in appetite and food intake and a decrease in physical
activity. Thus, our theory shows that obesity does not have to be caused by
overeating and sedentary life-style but may be the result of the "obese" change
in metabolism which is forcing people to overeat and save energy to sustain
metabolic functions of cells. This "obese" change is caused by environmental
factors that activate chronic low-grade inflammatory process in the body linking
obesity with the environment of developed countries.
PMID: 14559057 [PubMed]
128: Curr Opin Clin Nutr Metab Care. 2003 Nov;6(6):629-34.
Fats and food intake.
French S, Robinson T.
Masterfoods (a Division of Mars UK Ltd), Slough, UK. stephen.french@eu.effem.com
PURPOSE OF REVIEW: Given the global rates of obesity and the potential link to
dietary fat intake, understanding the role of fat in the regulation of food
intake is critical. Some short-term, laboratory-based studies demonstrate poor
compensation for manipulation of fat content, leading to passive
overconsumption, while others demonstrate compensation to levels similar to
other macronutrients. The observation of compensation in the short term does not
concur with long-term rates of obesity increase. This review discusses factors
that may explain at a physiological level these discrepancies, in particular fat
structure, dietary adaptation, and palatability. RECENT FINDINGS: Medium-chain
triglycerides have been demonstrated to be more satiating and promote weight
loss. Recent data suggest different gastrointestinal transduction mechanisms
elicit vagal afferent firing for fatty acids of different chain length. Dietary
adaptation to fat can influence the sensitivity of the feedback response, which
appears to be nutrient specific and relate to gastric emptying rates and
hormonal feedback. Fat content has been found to influence palatability of
foods. Recently it has been demonstrated that increasing palatability can
partially override the satiating effects of covertly manipulated macronutrient
preloads. Recent data suggest that hormonal influences may also affect the
palatability response. SUMMARY: It is becoming increasingly clear that although
energy density of diets is a major factor determining intake, macronutrient
structure, subject, dietary and taste differences can all play an important
modulatory influence on the final response on food intake. Further understanding
of these factors and interactions may provide strategies to help aid weight
regulation.
PMID: 14557792 [PubMed]
129: Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R1011-20.
Central leptin gene therapy fails to overcome leptin resistance associated with
diet-induced obesity.
Wilsey J, Zolotukhin S, Prima V, Scarpace PJ.
Geriatric Research, Education and Clinical Center, Dept. of Veterans Affairs
Medical Center, Gainesville, FL 32608-1197, USA.
The objective of this study was to determine if central overexpression of leptin
could overcome the leptin resistance caused by 100 days of high-fat feeding.
Three-month old-F344XBN male rats were fed either control low fat chow (Chow),
which provides 15% of energy as fat, or a high-fat/high-sucrose diet (HF), which
provides 59% of energy as fat. Over several weeks, the HF-fed animals
spontaneously split into two groups of animals: those that became obese on the
HF diet (DIO) and those that did not gain extra weight on the HF diet [diet
resistant (DR)]. After 100 days of HF feeding, animals were given a single
intracerebroventricular injection containing 5.75E10 particles of rAAV encoding
leptin (rAAV-leptin) or control virus (rAAV-con). Chow animals responded
robustly to rAAV-leptin, including significant anorexia, weight loss, and
lipopenia. In contrast, DIO were completely unresponsive to rAAV-leptin. DR rats
responded to rAAV-leptin, but in a more variable fashion than Chow. Unlike what
was observed in Chow, the anorectic response to rAAV-leptin rapidly attenuated
and was no longer significant by day 14 postvector delivery. Both DIO and DR
animals were found to have reduced long-form leptin receptor expression and
enhanced basal P-STAT-3 in the hypothalamus with respect to Chow. rAAV-leptin
caused an increase in STAT3 phosphorylation and proopiomelanocortin expression
in the hypothalamus and an increase in uncoupling protein-1 in brown adipose
tissue in both Chow and DR animals, but failed to do so in DIO. This suggests
that central overexpression of leptin is not a viable strategy to reverse
diet-induced obesity.
PMID: 14557234 [PubMed]
130: J Anim Sci. 2003 Oct;81(10):2515-24.
Effect of chromium propionate on growth, carcass traits, pork quality, and
plasma metabolites in growing-finishing pigs.
Shelton JL, Payne RL, Johnston SL, Bidner TD, Southern LL, Odgaard RL, Page TG.
Department of Animal Sciences, Louisiana State University Agricultural Center,
Baton Rouge 70803-4210, USA.
Two experiments were conducted to determine the effects of dietary Cr, as Cr
propionate, on growth, carcass traits, pork quality, and plasma metabolites in
growing-finishing swine. Ninety-six crossbred gilts (Exp. 1; initial and final
BW of 28 [SEM = 0.41] and 109 [SEM = 2.11] kg) or 144 PIC Cambrough 22 barrows
(Exp. 2; initial and final BW of 26 [SEM = 0.39] and 111 [SEM = 2.52] kg) were
allotted to six or four dietary treatments, respectively, with six replications
and four (Exp. 1) or six (Exp. 2) pigs in each replicate pen blocked by weight
in randomized complete block designs. The six dietary treatments for Exp. 1 were
1) corn-soybean meal (C-SBM), 2) C-SBM + 50 ppb Cr, 3) C-SBM + 100 ppb Cr, 4)
C-SBM + 200 ppb Cr, 5) C-SBM low NE diet, and 6) C-SBM low NE diet + 200 ppb Cr.
The four dietary treatments for Exp. 2 were C-SBM with 0, 100, 200, or 300 ppb
Cr. Growth, carcass traits, and plasma metabolite (collected on d 29 and at each
phase change) data were taken at the end of both experiments and pork quality
data were taken at the end of Exp. 1. There was no effect (P > 0.10) on overall
growth performance when pigs were fed graded levels of Cr (Exp. 1 and 2) or Cr
in the positive control or low NE diets (Exp. 1). Longissimus muscle area, ham
weight, ham fat-free lean, and total carcass lean were increased in pigs fed 200
ppb in the positive control diets but decreased in pigs fed 200 ppb Cr in the
low NE diets (Cr x NE, P < 0.08). There was no effect of Cr concentration (P >
0.10) on carcass traits in Exp. 2. In Exp. 1, cook loss of a fresh or a frozen
chop was decreased (P < 0.10) by 200 ppb Cr. In Exp. 1, NEFA concentration was
decreased (P < 0.05) in pigs fed Cr in the positive control or low NE diets
during the early-finishing period. In Exp. 2, the addition of Cr decreased NEFA
(quadratic, P < 0.09) and plasma urea N (linear, P < 0.02) concentrations and
tended to increase total cholesterol and high density lipoproteins (quadratic, P
< 0.09). In these experiments, Cr propionate had no effect on overall growth
performance, variable effects on carcass traits and plasma metabolites, and some
positive effects on pork quality, especially water holding capacity of a fresh
or frozen chop.
PMID: 14552379 [PubMed]
131: Endocrinology. 2004 Jan;145(1):243-52. Epub 2003 Oct 09.
Impaired coordination of nutrient intake and substrate oxidation in
melanocortin-4 receptor knockout mice.
Albarado DC, McClaine J, Stephens JM, Mynatt RL, Ye J, Bannon AW, Richards WG,
Butler AA.
Pennington Biomedical Research Center/Louisiana State University, Baton Rouge,
Louisiana 70808, USA.
Mutations in the melanocortin-4 receptor (MC4R) are associated with obesity. The
obesity syndrome observed in humans with MC4R haploinsufficiency is similar to
that observed in MC4R knockout mice, including increased longitudinal growth,
hyperphagia, and fasting hyperinsulinemia. For comparison with other commonly
investigated models of obesity and insulin resistance, we have backcrossed
Mc4r-/- mice into the C57BL/6J (B6) background. Female obese Mc4r-/- mice
exhibit reduced energy expenditure and an attenuated increase in fatty acid (FA)
oxidation after exposure to high-fat diets compared with obese Lepob/Lepob mice.
The reduced energy expenditure and FA oxidation correlates with changes in
hepatic gene expression. The expression of genes involved in FA oxidation
increased in obese Lepob/Lepob mice compared with wild-type and obese Mc4r-/-
mice. In contrast, a key lipogenic enzyme, FA synthase (FAS), is increased in
obese Mc4r-/- mice compared with obese Lepob/Lepob mice. Hyperinsulinemia,
increased FAS mRNA expression and hepatic steatosis appear to be secondary to
obesity in B6 Mc4r-/- mice. However, Mc4r-/- mice in a mixed genetic background
develop severe hepatic steatosis at an early age. This might suggest an
important role of the MC4R in regulating liver FA metabolism that is masked on
the B6 background. Interestingly, the 10- to 20-fold increase in liver
triglyceride in the outbred strain of Mc4r-/- mice is not always associated with
fasting hyperinsulinemia or increased FAS mRNA expression. This observation
suggests that changes in liver secondary to triglyceride accumulation lead to
hyperinsulinemia and increased hepatic FAS expression in Mc4r-/- mice.
PMID: 14551222 [PubMed]
132: Endocr Res. 2003 Aug;29(3):257-64.
The relation between serum leptin levels and body fat mass in patients with
active lung tuberculosis.
Yuksel I, Sencan M, Dokmetas HS, Dokmetas I, Ataseven H, Yonem O.
Department of Internal Medicine, Faculty of Medicine, Cumhuriyet University,
Sivas, Turkey.
The relationship of leptin to diminished appetite and weight loss has been
investigated in many diseases. Diminished appetite and weight loss are the most
apparent characteristics of patients with active lung tuberculosis and in this
study the relation of leptin to such diminished appetite and weight loss has
been investigated in patients with active lung tuberculosis before and after
treatment. Twenty-five patients (7 female, 18 male) with active tuberculosis
having an age range of 18-70 years (mean 47.48 +/- 15.36 y) and 25 normal
individuals (9 female, 16 male) having an age range of 25-71 years (mean 44.60
+/- 13.80 y) were included in this study. Leptin levels, body mass index (BMI),
body fat ratio (BFR), and waist hip ratio (WHR) were measured before and after 6
months of antituberculosis treatment. The same measurements were also made in
the control group and the results were compared. While the pretreatment BMI
(22.02 +/- 4.31 kg/m2) and BFR (16.60% +/- 9.30%) values in the patient group
were significantly lower than in the control group, we found no difference in
their pretreatment WHR values. Pretreatment leptin levels (3.49 +/- 3.34
microg/L) were significantly higher in patients with tuberculosis than in the
control group (2.33 +/- 1.10 microg/L). Leptin levels were found to be
significantly increased at the 6th month of antituberculosis treatment (5.65 +/-
5.41 microg/L) than the pretreatment values (p < 0.05). We observed an evident
increase in BMI (24.10 +/- 4.87 kg/m2) and BFR (17.51% +/- 9.25%) due to
antituberculosis treatment (p < 0.05). This study suggests that leptin has a
role in the diminished appetite and weight loss symptoms in patients with active
lung tuberculosis.
PMID: 14535627 [PubMed]
133: J Nucl Med. 2003 Oct;44(10):1582-5.
Visualization of interscapular brown adipose tissue using (99m)Tc-tetrofosmin in
pediatric patients.
Fukuchi K, Ono Y, Nakahata Y, Okada Y, Hayashida K, Ishida Y.
Department of Radiology, National Cardiovascular Center, Suita, Osaka, Japan.
kfukuchi@hsp.ncvc.go.jp
Brown adipose tissue (BAT) is a site of nonshivering thermogenesis in mammals.
The mitochondria of BAT operate in an uncoupled mode and increase fatty acid
oxidation to produce heat at birth. Thus, the BAT of human infants and children
contains more active mitochondria than that of adults. We surmised that because
(99m)Tc-tetrofosmin can be absorbed by functional mitochondria in the myocardium
and in tumor cells, it could reveal mitochondrial function in BAT. METHODS:
Between January 1999 and December 2002, we retrospectively analyzed 385
consecutive studies of (99m)Tc-tetrofosmin uptake in pediatric patients with
cardiac disorders. All patients with symmetric (99m)Tc-tetrofosmin accumulation
within the neck and shoulder region according to planar images were selected,
and the features of the uptake were analyzed. RESULTS: Increased symmetric
(99m)Tc-tetrofosmin uptake in the interscapular BAT was a typical profile of 65
of the 385 patients (17%). The frequency of (99m)Tc-tetrofosmin uptake was
significantly higher in winter than in spring or summer (P < 0.05) and prominent
in newborns. The frequency peaked between 0 and 2 y of age and then declined
with age. CONCLUSION: Gamma-camera imaging with (99m)Tc-tetrofosmin can reveal
interscapular BAT distribution in infants and children in terms of mitochondrial
activity.
Publication Types:
Evaluation Studies
PMID: 14530470 [PubMed]
134: J Am Dent Assoc. 2003 Sep;134(9):1185-92.
Tooth loss and dietary intake.
Hung HC, Willett W, Ascherio A, Rosner BA, Rimm E, Joshipura KJ.
Department of Epidemiology, Harvard School of Public Health, Boston, USA.
BACKGROUND: Several studies have reported that impaired dentition status is
associated with poor nutritional intake. However, most of these studies are
cross-sectional and thus are unable to clarify the temporal sequence. METHODS:
We assessed the longitudinal relation between tooth loss and changes in
consumption of fruits and vegetables and of nutrients important for general
health among 31,813 eligible male health professionals. RESULTS: Subjects who
lost five or more teeth had a significantly smaller reduction in consumption of
dietary cholesterol and vitamin B12, greater reduction in consumption of
polyunsaturated fat and smaller increase in consumption of dietary fiber and
whole fruit than did subjects who had lost no teeth. Men who had lost teeth also
were more likely to stop eating apples, pears and raw carrots. CONCLUSIONS: The
results support the temporal association between tooth loss and detrimental
changes in dietary intakes, which could contribute to increased risk of
developing chronic diseases. PRACTICE IMPLICATIONS: Dietary evaluation and
recommendations can be incorporated into dental visits to provide a greater
benefit to patients.
PMID: 14528990 [PubMed]
135: FASEB J. 2003 Dec;17(15):2299-301. Epub 2003 Oct 02.
Peroxisome proliferator-activated receptor delta controls muscle development and
oxidative capability.
Luquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J, Rassoulzadegan M,
Grimaldi PA.
Inserm U470, Centre de Biochimie, Parc Valrose, Universite de Nice-Sophia
Antipolis, 06108 Nice cedex 2, France.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors
exerting several functions in development and metabolism. The physiological
functions of PPARdelta remain elusive. By using a CRE-Lox recombination
approach, we generated an animal model for muscle-specific PPARdelta
overexpression to investigate the role of PPARdelta in this tissue.
Muscle-specific PPARdelta overexpression results in a profound change in fiber
composition due to hyperplasia and/or shift to more oxidative fiber and, as a
consequence, leads to the increase of both enzymatic activities and genes
implicated in oxidative metabolism. These changes in muscle are accompanied by a
reduction of body fat mass, mainly due to a large reduction of adipose cell
size. Furthermore, we demonstrate that endurance exercise promotes an
accumulation of PPARdelta protein in muscle of wild-type animals. Collectively,
these results suggest that PPARdelta plays an important role in muscle
development and adaptive response to environmental changes, such as training
exercise. They strongly support the idea that activation of PPARdelta could be
beneficial in prevention of metabolic disorders, such as obesity or type 2
diabetes.
PMID: 14525942 [PubMed]
136: Am J Clin Nutr. 2003 Oct;78(4):873S-880S.
Sugars, hypertriglyceridemia, and cardiovascular disease.
Fried SK, Rao SP.
Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA.
sfried@grecc.umaryland.edu
Short-term studies consistently show that raising the carbohydrate content of
the diet increases serum triacylglycerol concentrations. As compared with
starches, sugars (particularly sucrose and fructose) tend to increase serum
triacylglycerol concentrations by approximately 60%. The magnitude of the effect
depends on other aspects of the diet, including the total amount of carbohydrate
and the types of fat, carbohydrate, and fiber, but definitive studies to
describe the dose-response relations are not available. Longer-term studies show
that some high-carbohydrate diets are not associated with increased fasting
serum triacylgycerol concentrations. However, sedentary subjects with upper-body
and visceral obesity who have the metabolic syndrome tend to be at higher risk
for hypertriglyceridemia in response to high-sucrose and high-carbohydrate
diets; moderate weight loss mitigates the effect. Hyperinsulinemia or insulin
resistance may play a role in promoting higher rates of VLDL synthesis and
hypertriglyceridemia in obesity, but the mechanisms remain unclear. The effect
of fructose in promoting triacylglycerol synthesis is independent of
insulinemia, however. In terms of the long-term effects of diets high in sugars
on the risk of cardiovascular disease, available epidemiologic evidence
indicates no association of sugars or total carbohydrate intake per se, but high
dietary glycemic load is associated with higher serum triacylglycerol
concentrations and greater risk of coronary heart disease in women. Studies are
needed to delineate the independent effects of dietary sugars and glycemic load
on serum triacylglycerol concentrations in lean and obese men and women and to
determine whether the elevations in fasting and fed concentrations of serum
triacylglycerol with high-carbohydrate and high-sugars diets are associated with
increased risk of cardiovascular disease.
Publication Types:
Review
Review, Tutorial
PMID: 14522752 [PubMed]
137: J Nutr. 2003 Oct;133(10):3141-4.
Fermentable and nonfermentable fiber supplements did not alter hunger, satiety
or body weight in a pilot study of men and women consuming self-selected diets.
Howarth NC, Saltzman E, McCrory MA, Greenberg AS, Dwyer J, Ausman L, Kramer DG,
Roberts SB.
Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on
Aging at Tufts University, Boston, MA 02111, USA.
Little is known about the relative effects of fermentable fiber (FF) vs.
nonfermentable fiber (NFF) on energy regulation in humans. We compared 27 +/-
0.6 g/d supplements of FF (pectin, beta-glucan) and NFF (methylcellulose) for
their ability to decrease ad libitum energy intake (EI) and hunger, increase
satiety and cause spontaneous body weight and fat losses. Men and women (n = 11)
aged 23-46 y, BMI 20.0-34.4 kg/m2, consumed first NFF and then FF for 3 wk each,
with a 4-wk washout period between phases. Daily satiety assessed with analog
scales was higher with NFF than FF (60.7 +/- 1.0 vs. 57.7 +/- 0.8 mm, P = 0.01).
However, there were no differences in reported EI (NFF < FF by 7%, P = 0.31, NFF
< baseline by 9.5%, P = 0.11), body weight (NFF 0.13 kg, P = 0.73; FF 0.13 kg, P
= 0.60) or fat percentage (NFF -0.3%, P = 0.56; FF -0.1%, P = 0.66) within
either phase. In contrast to findings in animals, NFF was more, rather than less
satiating than FF, and use of neither NFF nor FF preparations was associated
with body weight or fat loss. These pilot results suggest no role for short-term
use of FF and NFF supplements in promoting weight loss in humans consuming a
diet ad libitum.
Publication Types:
Clinical Trial
PMID: 14519798 [PubMed]
138: Diabet Med. 2003 Oct;20(10):823-7.
Response to treatment with rosiglitazone in familial partial lipodystrophy due
to a mutation in the LMNA gene.
Owen KR, Donohoe M, Ellard S, Hattersley AT.
Department of Diabetes and Vascular Medicine, Peninsula Medical School, Barrack
Road, Exeter EX2 5AX, UK. K.R.Owen@ex.ac.uk
BACKGROUND: Familial partial lipodystrophy (FPLD) is a monogenic form of
diabetes characterised by a dominantly inherited disorder of adipose tissue
associated with the loss of subcutaneous fat from the limbs and trunk, with
excess fat deposited around the face and neck. The lipodystrophy causes severe
insulin resistance, resulting in acanthosis nigricans, diabetes, dyslipidaemia,
and increased risk of cardiovascular disease. Preliminary results from animals
and man suggest that increasing subcutaneous fat by treatment with
thiazolidinediones should improve insulin resistance and the associated features
of this syndrome. CASE REPORT: We report a 24-year-old patient with FPLD caused
by a mutation in the LMNA gene (R482W) treated with 12 months of rosiglitazone.
Subcutaneous fat increased following rosiglitazone treatment as demonstrated by
a 29% generalised increase in skin-fold thickness. Leptin levels increased from
5.8 to 11.2 ng/ml. Compared with treatment on Metformin, there was an increase
in insulin sensitivity (HOMA S% 17.2-31.6) but no change in glycaemic control.
The lipid profile worsened during the follow-up period. CONCLUSION: This initial
case suggests that, for modification of cardiovascular risk factors, there are
no clear advantages in treating patients with FPLD with rosiglitazone despite
increases in subcutaneous adipose tissue. Larger series will be needed to
identify moderate beneficial effects and treatment may be more effective in
patients with generalised forms of lipodystrophy.
Publication Types:
Case Reports
PMID: 14510863 [PubMed]
139: Endocrinology. 2004 Jan;145(1):401-6. Epub 2003 Sep 18.
Bone is a target for the antidiabetic compound rosiglitazone.
Rzonca SO, Suva LJ, Gaddy D, Montague DC, Lecka-Czernik B.
Department of Geriatrics, Reynolds Center on Aging, University of Arkansas for
Medical Sciences, Little Rock, Arkansas 72205, USA.
Rosiglitazone is an FDA-approved oral antidiabetic agent for the treatment of
type 2 diabetes. This compound improves insulin sensitivity through the
activation of the nuclear receptor, peroxisome proliferator-activated
receptor-gamma (PPAR-gamma). In addition to sensitizing cells to insulin, the
PPAR-gamma2 isoform appears to be critical for the regulation of osteoblast and
adipocyte differentiation from common mesenchymal bone marrow progenitors. We
have demonstrated previously that PPAR-gamma2 activated with rosiglitazone acts
as a dominant inhibitor of osteoblastogenesis in murine bone marrow in vitro.
Here, we show that in vivo, rosiglitazone administration results in significant
bone loss. When rosiglitazone (20 microg/g body weight/d) was given to
6-month-old, nondiabetic C57BL/6 mice for 7 wk, a significant decrease in total
body bone mineral density was observed. Analysis of bone microarchitecture,
using micro-computed tomography, demonstrated a decrease in bone volume,
trabecular width, and trabecular number and an increase in trabecular spacing.
Histomorphometric analysis showed a decrease in bone formation rate, with a
simultaneous increase in fat content in the bone marrow. Changes in bone
morphology and structure were accompanied by changes in the expression of
osteoblast- and adipocyte-specific marker genes; the expression of the
osteoblast-specific genes Runx2/Cbfa1, Dlx5, and alpha1(I)collagen were
decreased, whereas the expression of the adipocyte-specific fatty acid binding
protein aP2, was increased. These in vivo data suggest that rosiglitazone
therapy may pose a significant risk of adverse skeletal effects in humans.
PMID: 14500573 [PubMed]
140: J Neurosci Res. 2003 Oct 1;74(1):134-41.
Docosahexaenoic acid membrane content and mRNA expression of acyl-CoA oxidase
and of peroxisome proliferator-activated receptor-delta are modulated in Y79
retinoblastoma cells differently by low and high doses of alpha-linolenic acid.
Langelier B, Furet JP, Perruchot MH, Alessandri JM.
Nutrition and Food Safety, Institut National de la Recherche Agronomique,
Jouy-en-Josas, France.
The mRNA expression levels of acyl-CoA oxidase (AOX), a key enzyme in
very-long-chain fatty acid peroxisomal oxidation, and of peroxisome
proliferator-activated receptor-delta (PPAR-delta), a nuclear receptor possibly
involved in the gene regulation of brain lipid metabolism, were determined in
human Y79 retinoblastoma cells by using real-time quantitative polymerase chain
reaction. Cells were dosed with alpha-linolenic acid (18:3n-3), the essential
metabolic precursor of the n-3 polyunsaturated fatty acid series that normally
gives rise through terminal peroxisomal oxidation to the synthesis of membrane
docosahexaenoic acid (22:6n-3, or DHA). The AOX and PPAR-delta relative
expression levels increased 2.3 and 3.4 times, respectively, upon dosing of
cells with 7 microM 18:3n-3, whereas AOX cDNA abundance decreased by 50% upon
dosing with 70 microM 18:3n-3. Concurrently, the DHA content increased by 23% in
the membrane ethanolamine-phosphoglycerides from cells dosed with 7 microM
18:3n-3, whereas it decreased by 38% upon dosing with 70 microM 18:3n-3. The
DHA's upstream precursors (20:5n-3 and 22:5n-3) both accumulated in cells dosed
with 7 or 70 microM 18:3n-3. The 18:3n-3-induced changes in membrane
phospholipid fatty acid composition support the hypothesis that the terminal
peroxisomal step of n-3 conversion is rate limiting in the Y79 line. The
concurrent 7 microM 18:3n-3-induced increase of mRNAs encoding for AOX and for
PPAR-delta suggests that 18:3n-3 (or its metabolites) at low concentration could
trigger its proper conversion to DHA, possibly through activation of
PPAR-delta-mediated transcription of AOX. Decreased membrane DHA content and
mRNA expression level of AOX in 70-microM 18:3n-3-dosed cells corroborated the
relationship between AOX expression and DHA synthesis and suggested that
simultaneous down-regulating events occurred at high concentrations of 18:3n-3.
Copyright 2003 Wiley-Liss, Inc.
PMID: 13130515 [PubMed]
141: Int J Obes Relat Metab Disord. 2003 Dec;27(12):1565-71.
Greater rise in fat oxidation with medium-chain triglyceride consumption
relative to long-chain triglyceride is associated with lower initial body weight
and greater loss of subcutaneous adipose tissue.
St-Onge MP, Jones PJ.
School of Dietetics and Human Nutrition, McGill University, Montreal, Quebec,
Canada. ms2554@columbia.edu
OBJECTIVE: Medium-chain triglyceride (MCT) consumption has been shown to
increase energy expenditure (EE) and lead to greater losses of the adipose
tissue in animals and humans. The objective of this research was to examine the
relationship between body composition and thermogenic responsiveness to MCT
treatment. DESIGN: Randomized, crossover, controlled feeding trial, with diets
rich in either MCT or long-chain triglyceride (LCT) (as olive oil) for periods
of 4 weeks each. SUBJECTS: A total of 19 healthy overweight men aged
(x+/-s.e.m.) 44.5+/-2.5 y with a body mass index of 27.8+/-0.5 kg/m(2).
MEASUREMENTS: EE and body composition were measured using indirect calorimetry
and magnetic resonance imaging, respectively, at the baseline and end point of
each feeding period. EE was measured for 30 min before consumption of a standard
meal and for 5.5 h following the meal. RESULTS: Body weight (BW) decreased
(P<0.05) by 1.03+/-0.25 kg with MCT consumption compared to 0.62+/-0.29 kg with
LCT consumption. The difference in average EE between MCT and LCT consumptions
was related to initial BW, such that men with lower initial BW had a greater
rise in EE with MCT consumption relative to LCT on day 28 (r=-0.472, P=0.04) but
not day 2 (r=-0.368, P=0.12). Similar results were obtained with fat oxidation
on day 28 (r=-0.553, P=0.01). The greater rise in fat oxidation with MCT
compared to LCT consumption on day 2 tended to be related to greater loss of BW
after MCT vs LCT consumption (r=-0.4075, P=0.08). CONCLUSION: These data suggest
that shunting of dietary fat towards oxidation results in diminished fat
storage, as reflected by the loss of BW and subcutaneous adipose tissue.
Furthermore, MCT consumption may stimulate EE and fat oxidation to a lower
extent in men of greater BW compared to men of lower BW, indicative of the lower
responsiveness to a rapidly oxidized fat by overweight men.International
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12975635 [PubMed]
142: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11696-701. Epub 2003 Sep 15.
Chronic stress and obesity: a new view of "comfort food".
Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, Bell ME,
Bhatnagar S, Laugero KD, Manalo S.
Department of Physiology and Neuroscience Program, University of California, San
Francisco, CA 94143-0444, USA. dallman@itsa.ucsf.edu
The effects of adrenal corticosteroids on subsequent adrenocorticotropin
secretion are complex. Acutely (within hours), glucocorticoids (GCs) directly
inhibit further activity in the hypothalamo-pituitary-adrenal axis, but the
chronic actions (across days) of these steroids on brain are directly
excitatory. Chronically high concentrations of GCs act in three ways that are
functionally congruent. (i) GCs increase the expression of
corticotropin-releasing factor (CRF) mRNA in the central nucleus of the
amygdala, a critical node in the emotional brain. CRF enables recruitment of a
chronic stress-response network. (ii) GCs increase the salience of pleasurable
or compulsive activities (ingesting sucrose, fat, and drugs, or wheel-running).
This motivates ingestion of "comfort food." (iii) GCs act systemically to
increase abdominal fat depots. This allows an increased signal of abdominal
energy stores to inhibit catecholamines in the brainstem and CRF expression in
hypothalamic neurons regulating adrenocorticotropin. Chronic stress, together
with high GC concentrations, usually decreases body weight gain in rats; by
contrast, in stressed or depressed humans chronic stress induces either
increased comfort food intake and body weight gain or decreased intake and body
weight loss. Comfort food ingestion that produces abdominal obesity, decreases
CRF mRNA in the hypothalamus of rats. Depressed people who overeat have
decreased cerebrospinal CRF, catecholamine concentrations, and
hypothalamo-pituitary-adrenal activity. We propose that people eat comfort food
in an attempt to reduce the activity in the chronic stress-response network with
its attendant anxiety. These mechanisms, determined in rats, may explain some of
the epidemic of obesity occurring in our society.
PMID: 12975524 [PubMed]
143: Plast Reconstr Surg. 2003 Sep 15;112(4):1032-9.
Improvement of TRAM flap viability using human VEGF-induced angiogenesis: a
comparative study of delay techniques.
Seify H, Bilkay U, Jones G.
Division of Plastic, Reconstructive, and Maxillofacial Surgery, Emory University
School of Medicine, Atlanta, GA 30308, USA.
Despite the success with transverse rectus abdominis musculocutaneous (TRAM)
flap breast reconstruction, ischemia-related complications, including fat
necrosis and partial flap loss, continue to occur in 5 to 28 percent of reported
series. The associated vascular problems of the TRAM flap stimulated several
authors to study the effect of surgical delay, aiming to improve the viability
of the flap. The present study investigated the potential effect of human
vascular endothelial growth factor (hVEGF) in the induction of angiogenesis in
the TRAM flap model and compared its effect with the surgical delay model. The
rat model was used to demonstrate the effect of VEGF angiogenesis. Thirty male
Sprague-Dawley rats were individually assigned to one of six groups (n = 5 in
each group). One control group and five delay groups were established. A variety
of flap delay techniques were used to increase the viable surface area of the
flap. The flap mean viable surface area for the control group was 50 percent.
The surgical delay group (group 2) had a mean viability of 83 percent. The group
with the highest percentage of viable flap surface area was group 3, in which
both surgical delay and intramuscular injection of VEGF were used (96.6 percent
mean flap viability). The mean viable flap surface area in groups 4 (surgical
delay and intraarterial VEGF), 5 (intramuscular VEGF), and 6 (intraarterial
VEGF) were 90.6 percent, 87 percent, 90.6 percent, respectively. Statistically
significant differences were obtained in all groups in comparison to the control
group (p < 0.05). No significant differences were seen among the five treatment
groups, however. The findings reported in the present study indicate that the
use of VEGF to improve the viability of the TRAM flap proved to be beneficial
and statistically significant in comparison to the control group.
PMID: 12973219 [PubMed]
144: Obes Res. 2003 Sep;11(9):1040-7.
Impact of diet-induced weight loss on the cardiac autonomic nervous system in
severe obesity.
Poirier P, Hernandez TL, Weil KM, Shepard TJ, Eckel RH.
Division of Endocrinology, Metabolism, and Diabetes, University of Colorado
Health Sciences Center, Denver, Colorado, USA. Paul.Poirier@crhl.ulaval.ca
OBJECTIVE: To determine the impact of diet-induced weight loss on cardiac
autonomic nervous system modulation and arrhythmias in subjects with severe
obesity and the influence of a high-fat or a high-carbohydrate diet regimen on
heart rate variability in reduced-obese individuals. RESEARCH METHODS AND
PROCEDURES: Eight severely obese subjects (BMI > or = 40.0 kg/m(2)) underwent a
3-month weight loss program followed by a 3-month reduced-weight maintenance
regimen. Thereafter, each subject was admitted for an inpatient period of 17
days on two separate occasions. A high-carbohydrate (60%) or high-fat (55%) diet
of appropriate energy content for weight maintenance was prescribed during each
inpatient phase. Heart rate variability was derived from a 24-hour Holter
monitoring system in all subjects during their inpatient stay. Cardiac Holter
monitoring was performed at three occasions (baseline, diet phase I, and diet
phase II), including the second night of a two overnight calorimetry chamber
stay. RESULTS: After the diet regimen, there was a 10% decrease in weight. There
were no significant changes in systolic and diastolic blood pressure,
arrhythmias, glucose, insulin, total cholesterol, low-density
lipoprotein-cholesterol, high-density lipoprotein-cholesterol, respiratory
exchange ratio, and resting energy expenditure between experiments. Mean heart
rate was lower after weight loss compared with baseline (p < 0.001). After
weight loss, there was an increase in the parasympathetic indices of heart rate
variability showing an increase in cardiac vagal modulation (all p < 0.05).
DISCUSSION: Weight loss is associated with significant improvement in autonomic
cardiac modulation through enhancement of parasympathetic modulation, which
clinically translates into a decrease in heart rate.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12972673 [PubMed]
145: J Appl Physiol. 2003 Oct;95(4):1728-36.
Invited review: Aging and energy balance.
Wilson MM, Morley JE.
Division of Geriatric Medicine, St. Louis Univ. School of Medicine, 1402 S.
Grand Blvd., M238, St. Louis, Missouri 63104, USA.
Humans over 70 yr of age often lose weight. This appears to be due to a
physiological anorexia of aging as well as a loss of lean mass (sarcopenia) and,
to a lesser extent, fat mass. The causes of the physiological anorexia of aging
include changes in taste and smell and a decrease in adaptive relaxation of the
fundus of the stomach, which leads to more rapid antral filling and early
satiation. In addition, basal and stimulated levels of the satiating hormone,
cholecystokinin, are increased. In men, the decline in testosterone leads to an
increase in leptin and a loss of lean mass. Although resting metabolic rate
declines with aging, this is mainly due to the decline in lean body mass. Energy
metabolism is also decreased due to a decline in Na+-K+-ATPase activity,
decreased muscle protein turnover, and possibly changes in mitochondrial
membrane protein permeability. Physical energy expenditure declines with aging.
Meal-induced thermogenesis shows a delay to peak, possibly due to a delay in
gastric emptying. Inadequate data are available on the effect of aging in humans
on other energy-producing mechanisms such as adaptive thermogenesis. These
physiological changes place older men and women at major risk of developing
pathological weight loss when they develop disease states, especially those
associated with cytokine elaboration.
Publication Types:
Review
Review, Tutorial
PMID: 12970378 [PubMed]
146: Gut. 2003 Oct;52(10):1479-86.
Comment in:
Gut. 2003 Oct;52(10):1391-2.
Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on
loss of weight and lean tissue in cancer cachexia: a randomised double blind
trial.
Fearon KC, Von Meyenfeldt MF, Moses AG, Van Geenen R, Roy A, Gouma DJ, Giacosa
A, Van Gossum A, Bauer J, Barber MD, Aaronson NK, Voss AC, Tisdale MJ.
Royal Infirmary of Edinburgh, Edinburgh, UK.
AIM: N-3 fatty acids, especially eicosapentaenoic acid (EPA), may possess
anticachectic properties. This trial compared a protein and energy dense
supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with
an isocaloric isonitrogenous control supplement (C) for their effects on weight,
lean body mass (LBM), dietary intake, and quality of life in cachectic patients
with advanced pancreatic cancer. METHODS: A total of 200 patients (95 E; 105 C)
were randomised to consume two cans/day of the E or C supplement (480 ml, 620
kcal, 32 g protein +/- 2.2 g EPA) for eight weeks in a multicentre, randomised,
double blind trial. RESULTS: At enrolment, patients' mean rate of weight loss
was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended
dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both
groups stopped losing weight (delta weight E: -0.25 kg/month versus C: -0.37
kg/month; p = 0.74) and LBM (Delta LBM E: +0.27 kg/month versus C: +0.12
kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001).
In view of evident non-compliance in both E and C groups, correlation analyses
were undertaken to examine for potential dose-response relationships. E patients
demonstrated significant correlations between their supplement intake and weight
gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such
correlations were not statistically significant in C patients. The relationship
of supplement intake with change in LBM was significantly different between E
and C patients (p = 0.043). Increased plasma EPA levels in the E group were
associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001).
Weight gain was associated with improved quality of life (p<0.01) only in the E
group. CONCLUSION: Intention to treat group comparisons indicated that at the
mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic
advantage and that both supplements were equally effective in arresting weight
loss. Post hoc dose-response analysis suggests that if taken in sufficient
quantity, only the n-3 fatty acid enriched energy and protein dense supplement
results in net gain of weight, lean tissue, and improved quality of life.
Further trials are required to examine the potential role of n-3 enriched
supplements in the treatment of cancer cachexia.
Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial
PMID: 12970142 [PubMed]
147: Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1626-31.
beta-Hydroxybutyrate inhibits myocardial fatty acid oxidation in vivo
independent of changes in malonyl-CoA content.
Stanley WC, Meadows SR, Kivilo KM, Roth BA, Lopaschuk GD.
Department of Physiology and Biophysics, School of Medicine, Case Western
Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4970, USA.
WCS4@po.cwru.edu
This study tested the hypothesis that an acute infusion of beta-hydroxybutyrate
inhibits myocardial fatty acid uptake and oxidation in vivo. Anesthetized pigs
were untreated (n = 6) or treated with an intravenous infusion of fat emulsion
(n = 7) to elevate plasma free fatty acid levels. A third group received fat
emulsion plus an intravenous infusion of beta-hydroxybutyrate (25
micromol.kg-1.min-1; n = 7) for 60 min. All animals received a continuous
infusion of [3H]palmitate, and myocardial fatty acid oxidation was measured from
the cardiac production of 3H2O. Plasma free fatty acid concentrations were
elevated in the fat emulsion group (0.77 +/- 0.11 mM) compared with the
untreated group (0.15 +/- 0.03 mM), which resulted in greater myocardial free
fatty acid oxidation. In contrast, the group receiving beta-hydroxybutyrate in
addition to fat emulsion had elevated beta-hydroxybutyrate concentration (0.87
+/- 0.11 vs. 0.04 +/- 0.01 mM), but suppressed fatty acid oxidation (0.053 +/-
0.013 micromol.g-1.min-1) (P < 0.05) compared with the fat emulsion group (0.116
+/- 0.029 micromol.g-1.min-1). There were no differences among the three groups
in the tissue content for malonyl-CoA, acetyl-CoA, or free CoA or the activity
of acetyl-CoA carboxylase; thus the inhibition of fatty acid oxidation by
elevated beta-hydroxybutyrate did not appear to be due to malonyl-CoA inhibition
of carnitine palmitoyl transferase-I or to an increase in the acetyl-CoA-to-free
CoA ratio. In conclusion, fatty acid uptake and oxidation is blocked by an
infusion of beta-hydroxybutyrate; this effect was not due to elevated myocardial
malonyl-CoA content.
PMID: 12969881 [PubMed]
148: J Anim Sci. 2003 Sep;81(9):2206-12.
Relationships between longissimus glycolytic potential and swine growth
performance, carcass traits, and pork quality.
Hamilton DN, Miller KD, Ellis M, McKeith FK, Wilson ER.
Department of Animal Sciences, University of Illinois, Urbana 61801, USA.
The relationships between glycolytic potential and growth performance, carcass
traits, and pork quality were investigated in a group of 72 pigs from the same
genetic line. Glycolytic potential (GP) was determined on live-animal biopsy
samples and postmortem samples taken from the longissimus muscle, and free
glucose concentration was measured on the exudate from the longissimus muscle
taken postmortem. The mean live-animal and postmortem GP and free glucose values
were 201.6 micromol/g (range = 113.8 to 301.1), 149.8 micromol/g (range = 91.0
to 270.5) and 110.1 mg/dL (range = 30.0 to 406.0), respectively. Correlations
between live-animal and postmortem GP and free glucose ranged from 0.47 to 0.70;
however, all three measures were weakly related to growth and carcass traits (r
= 0.03 to -0.22; P > 0.05). Correlations of GP and free glucose values with
fresh pork quality measurements were moderate (r = 0.23 [P < 0.05] to -0.63 [P <
0.001]). Regression analysis suggested that a one standard deviation increase in
live-animal and postmortem GP and free glucose resulted in an increase in L*
values (0.99, 1.32, and 2.05, respectively) and drip loss (0.85, 1.10, and 1.39
percentage units, respectively), as well as a decrease in ultimate pH (0.05,
0.11, and 0.16, respectively). Correlations between GP and cooking loss and
tenderness and juiciness scores ranged between 0.16 (P > 0.05) to 0.34 (P <
0.01). Free glucose concentration showed no relationship (P > 0.05) with cooking
loss, tenderness, and juiciness. Regression analysis suggested that a one
standard deviation increase in live-animal and postmortem GP increased cooking
loss (1.26% and 1.65%, respectively) and would improve taste panel tenderness
(0.54 and 0.44, respectively) and juiciness (0.40 and 0.48, respectively)
scores. Increasing GP and free glucose was also associated with decreased
longissimus fat and protein, and increased moisture contents (r = 0.14 [P >
0.05] to -0.45 [P < 0.001]). Overall, relationships with fresh meat quality
characteristics were stronger for free glucose values than either live-animal or
postmortem GP. Results from this study indicate that decreasing longissimus GP
and free glucose concentrations may improve pork color and water-holding
capacity.
PMID: 12968695 [PubMed]
149: J Bone Miner Res. 2003 Sep;18(9):1650-6.
Determinants of bone density in 30- to 65-year-old women: a co-twin study.
MacInnis RJ, Cassar C, Nowson CA, Paton LM, Flicker L, Hopper JL, Larkins RG,
Wark JD.
Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia.
Reported effects of body composition and lifestyle on bone mineral density in
pre-elderly adult women have been inconsistent. In a co-twin study, we measured
bone mineral density, lean and fat mass, and lifestyle factors. Analyzing within
pair differences, we found negative associations between bone mineral density
and tobacco use (2.3-3.3% per 10 pack-years) and positive associations with
sporting activity and lean and fat mass. INTRODUCTION: Reported effects of body
composition and lifestyle of bone mineral density in pre-elderly adult women
have been inconsistent. METHODS: In a co-twin study of 146 female twin pairs
aged 30 to 65 years, DXA was used to measure bone mineral density at the lumbar
spine, total hip, and forearm, total body bone mineral content, and lean and fat
mass. Height and weight were measured. Menopausal status, dietary calcium
intake, physical activity, current tobacco use, and alcohol consumption were
determined by questionnaire. Within-pair differences in bone measures were
regressed through the origin against within-pair differences in putative
determinants. RESULTS: Lean mass and fat mass were associated with greater bone
mass at all sites. A discordance of 10 pack-years smoking was related to a
2.3-3.3% (SE, 0.8-1.0) decrease in bone density at all sites except the forearm,
with the effects more evident in postmenopausal women. In all women, a 0.8% (SE,
0.3) difference in hip bone mineral density was associated with each hour per
week difference in sporting activity, with effects more evident in premenopausal
women. Daily dietary calcium intake was related to total body bone mineral
content and forearm bone mineral density (1.4 +/- 0.7% increase for every 1000
mg). Lifetime alcohol consumption and walking were not consistently related to
bone mass. CONCLUSION: Several lifestyle and dietary factors, in particular
tobacco use, were related to bone mineral density. Effect sizes varied by site.
Characterization of determinants of bone mineral density in midlife and
thereafter may lead to interventions that could minimize postmenopausal bone
loss and reduce osteoporotic fracture risk.
Publication Types:
Twin Study
PMID: 12968674 [PubMed]
150: J Endocrinol. 2003 Sep;178(3):533-9.
GH and ghrelin increase with fasting in a naturally adapted species, the
northern elephant seal (Mirounga angustirostris).
Ortiz RM, Noren DP, Ortiz CL, Talamantes F.
Department of Biology, University of California, Santa Cruz, California 95064,
USA. rortiz1@tulane.edu
After nursing, pups of the northern elephant seal (Mirounga angustirostris) are
approximately 46% body fat and rely almost entirely on the oxidation of their
large fat stores to sustain their metabolism for the ensuing 8-12 week
postweaning fast, which is a natural component of their life history. Thus,
fasting pups provide an ideal opportunity to examine the hormonal alterations
associated with prolonged food deprivation in a naturally adapted model.
Cortisol, ghrelin, glucagon, growth hormone (GH), insulin-like growth factor-I
(IGF-I), insulin, blood urea nitrogen (BUN), glucose and non-esterified fatty
acids (NEFA) were examined in 20 male and 20 female pups blood sampled early (<1
week postweaning) and late (6-8 weeks postweaning) during the fast. Mean
cortisol, ghrelin, GH, and glucagon increased 1.8-, 1.8-, 1.4-, and 2.3-fold
between early and late periods, while mean IGF-I and insulin decreased 97% and
38%, respectively. NEFA increased 2.3-fold, while BUN and glucose decreased 46%
and 11%, respectively. NEFA was significantly and positively correlated with
cortisol and GH; individually; however, when the relationship was examined as a
multiple regression the correlation improved suggesting that cortisol and GH act
synergistically to promote lipolysis during the fast. GH and BUN were negatively
and significantly correlated between early and late fasting suggesting that GH
may promote protein sparing as well. The decrease in glucose may be responsible
for stimulating glucagon, resulting in the maintenance of relative
hyperglycemia. The increases in cortisol, ghrelin, glucagon, and GH suggest that
these hormones may be integral in mediating the metabolism of seal pups during
prolonged fasting.
PMID: 12967344 [PubMed]
151: Maturitas. 2003 Sep 25;46(1):59-68.
Body composition, visceral fat distribution and fat oxidation in postmenopausal
women using oral or transdermal oestrogen.
dos Reis CM, de Melo NR, Meirelles ES, Vezozzo DP, Halpern A.
Department of Endocrinology and Metabolism, School of Medicine, University of
Sao Paulo, Rua Guatemala 209, Jardim America, Sao Paulo, SP 01437-050, Brazil.
vitalita@uol.com.br
OBJECTIVES: The aim of this study was to observe hysterectomized postmenopausal
women (without progestogen, which could interfere in the results), using
oral-conjugated oestrogen 0.625 mg daily (n=13) or 17beta-estradiol transdermal
patches delivering 50 microg daily (n=10) during 12 months, and to evaluate the
treatment effects on body composition, visceral fat distribution, energy
expenditure and substrate oxidation. METHODS: We studied 23 postmenopausal women
using oral-conjugated oestrogen (Premarin) 0.625 mg daily (n=13) or transdermal
oestrogen patches (Systen TTS) 50 microg daily (n=10). Body composition was
measured by DEXA, visceral adipose tissue areas were measured by abdominal
computed tomography, and energy expenditure, fat oxidation and carbohydrate
oxidation were measured by indirect calorimetry (Deltatrac Metabolic Monitor).
RESULTS: There were: (1) a decrease in IGF-I and an increase in GH levels in the
oral group and no change in the transdermal group; (2) a increase in lean body
mass in the transdermal group and a decrease in the oral group; (3) a increase
in total body fat mass in the oral group and no change in the transdermal group;
(4) an increases in total bone mass and in total bone mineral density in the
transdermal group and no change in the oral group; (5) an increase in lipid
oxidation in the transdermal group and a decrease in the oral group, and (6) no
significantly change about weight, visceral adipose tissue areas and energy
expenditure in both groups. CONCLUSIONS: The administration route of oestrogen
replacement therapy in postmenopausal women confers distinct and divergent
effects on body composition and substrate oxidation during 12-months treatment.
Publication Types:
Clinical Trial
PMID: 12963170 [PubMed]
152: Endocrinology. 2003 Dec;144(12):5159-65. Epub 2003 Sep 04.
Minireview: weapons of lean body mass destruction: the role of ectopic lipids in
the metabolic syndrome.
Unger RH.
Touchstone Center for Diabetes Research, University of Texas Southwestern
Medical Center, 5323 Harry Hines Boulevard, Y8.212, Dallas, Texas 75390-8854,
USA. roger.unger@utsouthwestern.edu.
The obesity crisis in the United States has been associated with an alarming
increase in the prevalence of the metabolic syndrome (MSX) disease cluster. Here
we review evidence that the MSX reflects a failure of a system of intracellular
lipid homeostasis that prevents lipotoxicity in the organs of overnourished
individuals by confining the lipid overload to cells specifically designed to
store large quantities of surplus calories, the white adipocytes. Normally,
early in obesity, adipocytes increase leptin and adiponectin secretion, hormones
that enhance oxidation of surplus liquids in nonadipose tissues by activating
AMP-activated protein kinase and reducing the activity and expression of
lipogenic enzymes. These events combine to lower malonyl coenzyme A. Deficiency
of and/or unresponsiveness to leptin prevents these protective events and
results in ectopic accumulation of lipids. Increased de novo ceramide formation
is probably the most damaging lipid and is a cause of lipoapoptosis, abetted by
a decline in tissue Bcl-2. Pancreatic beta-cells and myocardiocytes are cellular
victims of the process, leading to non-insulin-dependent diabetes and lipotoxic
cardiomyopathy. The MSX is particularly prevalent in visceral obesity, probably
because visceral adipocytes make less leptin than sc adipocytes. Cushing's
syndrome, the lipodystrophy associated with protease inhibitor therapy of AIDS,
polycystic ovarian disease, as well as diet-induced visceral obesity, all have a
high waist/hip ratio, and all exhibit MSX. Increased lipid content in the heart
and skeletal muscle organs of such patients is now under study.
Publication Types:
Review
Review, Tutorial
PMID: 12960011 [PubMed]
153: Hepatol Res. 2003 Sep;27(1):45-50.
Effect of a late evening snack on the blood glucose level and energy metabolism
in patients with liver cirrhosis.
Okamoto M, Sakaida I, Tsuchiya M, Suzuki C, Okita K.
Department of Gastroenterology and Hepatology, Yamaguchi University School of
Medicine, Minami Kogushi 1-1-1, 755-8505, Yamaguchi Pref., Ube, Japan
BACKGROUND/AIM: Patients with liver cirrhosis suffer from energy malnutrition.
Late evening snacks (LESs) have been recently reported to be effective for this.
However, it is known that a significant proportion of patients with liver
cirrhosis have glucose intolerance as a complication. For this reason, the
influence of LES on the blood glucose level should be examined. SUBJECTS/METHOD:
We administered an oral supplement with branched-chain amino acids (Aminoleban
EN) to patients with liver cirrhosis at 10 P.M. to investigate the changes of
the blood glucose level and energy metabolism with an indirect calorimeter. Ten
patients (average age, 70; Child A/B/C, 5/4/1) participated in this study. The
administration period was 7 days. Blood glucose levels were examined before and
after breakfast, lunch, supper and at 10 P.M. RESULTS: (1) The fat oxidation
rate was significantly decreased and the carbohydrate oxidation rate
significantly increased. As a result, RQ was significantly improved. (2) With
many cases, an increase of glucose level after meals seemed to reduce with LES
administration for 1 week. (3) BTR was significantly improved. CONCLUSIONS: LES
could improve energy malnutrition, correct amino acid imbalance, and ultimately
may improve glucose intolerance in patients with liver cirrhosis.
PMID: 12957206 [PubMed]
154: J Surg Res. 2003 Aug;113(2):217-21.
Recovery of insulin sensitivity in obese patients at short term after
biliopancreatic diversion.
Adami GF, Cordera R, Camerini G, Marinari GM, Scopinaro N.
Department of Surgery, University of Genoa School of Medicine, Italy.
adami@unige.it
OBJECTIVE: To gain insight into the specific mechanisms by which biliopancreatic
diversion (BPD) can improve insulin action. MATERIALS AND METHODS: Nondiabetic
severely obese patients (n=20) undergoing BPD were included. Waist-to-hip ratio
and serum concentration of glucose, insulin, and leptin were determined before,
at 4-day, and at 2 months after the operation. Insulin sensitivity was
calculated according to the homeostatic model assessment (HOMA IR). RESULTS: A
marked increase of insulin sensitivity was observed by the fourth day after the
operation; at the second postoperative month, when body weight was still in the
obese range and the food intake was substantially similar to the preoperative
one, a further improvement of insulin action towards normality was found.
Moreover, before BPD HOMA IR data were independently correlated both to BMI and
waist-to-hip ratio values, whereas at 2 months after the operation data were in
positive correlation only with the BMI. DISCUSSION: In obese patients, BPD seems
to achieve recovery of insulin sensitivity by specific mechanisms independent of
weight loss: the main causes of this sharp improvement might be both the
intramyocellular fat depletion and the interruption of enteroinsular axis.
PMID: 12957132 [PubMed]
155: Am J Physiol Endocrinol Metab. 2003 Dec;285(6):E1230-6. Epub 2003 Sep 03.
White adipose tissue contributes to UCP1-independent thermogenesis.
Granneman JG, Burnazi M, Zhu Z, Schwamb LA.
Center for Integrative Metabolic and Endocrine Research, Department of
Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201,
USA. jgranne@med.wayne.edu
Beta3-adrenergic receptors (AR) are nearly exclusively expressed in brown and
white adipose tissues, and chronic activation of these receptors by selective
agonists has profound anti-diabetes and anti-obesity effects. This study
examined metabolic responses to acute and chronic beta3-AR activation in
wild-type C57Bl/6 mice and congenic mice lacking functional uncoupling protein
(UCP)1, the molecular effector of brown adipose tissue (BAT) thermogenesis.
Acute activation of beta3-AR doubled metabolic rate in wild-type mice and
sharply elevated body temperature and BAT blood flow, as determined by laser
Doppler flowmetry. In contrast, beta3-AR activation did not increase BAT blood
flow in mice lacking UCP1 (UCP1 KO). Nonetheless, beta3-AR activation
significantly increased metabolic rate and body temperature in UCP1 KO mice,
demonstrating the presence of UCP1-independent thermogenesis. Daily treatment
with the beta3-AR agonist CL-316243 (CL) for 6 days increased basal and
CL-induced thermogenesis compared with naive mice. This expansion of basal and
CL-induced metabolic rate did not require UCP1 expression. Chronic CL treatment
of UCP1 KO mice increased basal and CL-stimulated metabolic rate of epididymal
white adipose tissue (EWAT) fourfold but did not alter BAT thermogenesis. After
chronic CL treatment, CL-stimulated thermogenesis of EWAT equaled that of
interscapular BAT per tissue mass. The elevation of EWAT metabolism was
accompanied by mitochondrial biogenesis and the induction of genes involved in
lipid oxidation. These observations indicate that chronic beta3-AR activation
induces metabolic adaptation in WAT that contributes to beta3-AR-mediated
thermogenesis. This adaptation involves lipid oxidation in situ and does not
require UCP1 expression.
PMID: 12954594 [PubMed]
156: Int J Vitam Nutr Res. 2003 Jul;73(4):275-83.
Effects of megadoses of dietary vitamin E on the antioxidant status of rats fed
lard or salmon oil.
Flader D, Brandsch C, Hirche F, Eder K.
Institute of Nutritional Sciences, Martin-Luther-University Halle-Wittenberg,
Emil-Abderhalden-Strasse 26, 06108 Halle/Saale, Germany.
This study was undertaken to investigate whether megadoses of vitamin E in the
diet of rats can have pro-oxidative activity. Two experiments with rats were
conducted in which both the dietary vitamin E concentration (Experiment 1: 100;
500; 3000; 10,000 mg all-rac-alpha-tocopheryl acetate/kg, and Experiment 2: 100;
1000; 10,000 mg all-rac-alpha-tocopheryl acetate/kg) and the type of dietary fat
(lard vs. salmon oil) were varied. Experimental parameters were the
concentrations of thiobarbituric acid-reactive substances, 7
beta-hydroxycholesterol, the activities of several antioxidative enzymes, the
concentration of glutathione in the liver, and the lag time during
copper-induced low-density lipoprotein (LDL) oxidation. Increasing the dietary
vitamin E concentration to 10,000 mg all-rac-alpha-tocopheryl acetate/kg led to
a significant reduction of thiobarbituric acid-reactive substances in the liver
after feeding salmon oil, and also to a significant reduction in 7
beta-hydroxycholesterol after feeding both dietary fats. Megadoses of vitamin E
(3000 and 10,000 mg all-rac-alpha-tocopheryl acetate/kg) also led to a reduction
in the activity of superoxide dismutase and the concentration of glutathione in
the liver of rats fed salmon oil. The lag time during LDL oxidation was
independent of the dietary vitamin E concentration. The study shows that
megadoses of vitamin E, far from having pro-oxidative activity, actually
increase the anti-oxidative capacity of the liver, especially after ingestion of
salmon oil.
PMID: 12951900 [PubMed]
157: Exp Clin Endocrinol Diabetes. 2003 Aug;111(5):278-82.
Serum leptin monitoring in anorectic patients during refeeding therapy.
Lob S, Pickel J, Bidlingmaier M, Schaaf L, Backmund H, Gerlinghoff M, Stalla GK.
Max-Planck-Institute of Psychiatry, Munich, Germany.
simone.lob@stud.uni-muenchen.de
Circulating concentrations of leptin are exceedingly low in severe malnutrition
as seen in the acute state of anorexia nervosa (AN). During refeeding therapy
plasma leptin levels increase to normal and in some cases peak at values in
excess of the BMI of matched controls even before a normal body weight has been
achieved. Peak leptin levels are possibly the cause of an increased energy
expenditure during this stage of the disorder and might predispose to renewed
weight loss (rebound phenomenon). In this study we investigated the role of
leptin fluctuations as a prognostic factor of therapeutic success in AN. In 11
anorectic female patients serum leptin levels, BMI and body fat percentage were
evaluated in four-week intervals during a conventional refeeding program over
three months (group 1). The results of the first two measurements were used to
determine a range of increases in leptin levels in relation to increases in BMI.
The values between the 25th and 75th percentiles determined the reference range.
In a second group of 9 anorectic female patients serum leptin levels, BMI, body
fat percentage and the increase in the leptin level in relation to the BMI of
each subject were investigated for three months every two weeks. These patients
were also treated according to the same conventional refeeding program, but the
caloric intake was reduced or increased (+/-250 kcal/d) if the increase in the
leptin level, in relation to the increase in the BMI, had exceeded or fallen
short of the reference range. During the refeeding therapy every subject of each
group experienced increases in serum leptin levels, BMI and body fat percentage.
Six subjects of group 1 and six subjects of the second group had an increase in
leptin levels in relation to the increase of the BMI out of the reference range
at least once. To investigate the therapeutic outcome of leptin monitoring and
the following alteration of caloric intake, weight gain of the patients of both
groups during the whole treatment was compared. No significant difference was
found. Our results probably do not support the findings that high leptin levels
predispose to a renewed loss of weight. The outcome in our patients whose
caloric intake was modified due to their serum leptin levels was not
significantly improved.
Publication Types:
Clinical Trial
PMID: 12951634 [PubMed]
158: Biol Pharm Bull. 2003 Sep;26(9):1239-44.
Effect of supplementation of n-3 polyunsaturated fatty acids on oxidative
stress-induced DNA damage of rat hepatocytes.
Kikugawa K, Yasuhara Y, Ando K, Koyama K, Hiramoto K, Suzuki M.
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.
kikugawa@ps.toyaku.ac.jp
The effect of supplementation of n-3 polyunsaturated fatty acids (PUFA) on
oxidative stress-induced DNA damage of rat hepatocytes was examined. Male Wistar
rats were fed a diet containing safflower oil (control n-6 PUFA diet) or fish
oil (n-3 PUFA diet) in 50 g/kg of dried diet and an equal amount of vitamin E in
59 mg/kg of dried diet for 6 weeks. The liver of rats fed safflower oil was rich
in n-6 PUFA, whereas that of rats fed fish oil was rich in n-3 PUFA. Isolated
hepatocytes were treated in vitro with ADP/Fe (II) ion or hydrogen peroxide at
37 degrees C for 30 min to induce oxidative stress. The degree of lipid
peroxidation was assessed by the levels of phospholipid hydroperoxides and
thiobarbituric acid-reactive substances. The degree of oxidative DNA damage was
assessed based on comet-type characterization in alkaline single-cell gel
electrophoresis and 8-hydroxy-deoxyguanosine levels. In both ADP/Fe(II) ion and
hydrogen peroxide oxidation, the degree of lipid peroxidation of hepatocytes
increased in both diet groups, and the level of increase in the fish oil diet
group was slightly higher than that in the safflower oil diet group. In
ADP/Fe(II) ion oxidation, the degree of DNA damage increased in both diet
groups, but there were no significant differences in the level of increase. In
contrast, in hydrogen peroxide oxidation, the degree of DNA damage increased in
both diet, and the increase in the fish oil diet group was significantly lower
than that in the safflower oil diet group. It is unlikely that an n-3 PUFA-rich
diet enhances oxidative stress-induced hepatocyte DNA damage as compared with
the control n-6 PUFA-rich diet.
PMID: 12951465 [PubMed]
159: J Nutr. 2003 Sep;133(9):2830-7.
Thermally oxidized dietary fats increase the susceptibility of rat LDL to lipid
peroxidation but not their uptake by macrophages.
Eder K, Keller U, Hirche F, Brandsch C.
Institute of Nutritional Sciences, Martin-Luther-University of Halle-Wittenberg,
Emil-Abderhalden-Strassse 26, D-06108 Halle/Saale, Germany.
eder@landw.uni.halle.de
The aim of this study was to investigate the effect of dietary oxidized fats on
the lipoprotein profile and the atherogenicity of LDL. Two experiments with male
Sprague-Dawley rats were conducted. In Experiment 1, diets with either fresh fat
or oxidized fat, prepared by heating at temperatures of 50, 105 or 190 degrees
C, containing either 25 or 250 mg alpha-tocopherol equivalents/kg were used. In
Experiment 2, diets with fresh or oxidized fat, heated at a temperature of 55
degrees C, containing 25 mg alpha-tocopherol equivalents/kg, were used. In
Experiment 1, rats fed all types of oxidized fats had higher concentrations of
HDL cholesterol and lower ratios between plasma and HDL cholesterol than rats
fed the diet containing the fresh fat. As determined from the lag time, the
susceptibility of LDL to copper-induced lipid peroxidation was higher in rats
fed oxidized fats heated at 105 or 190 degrees C than in rats fed the diets
containing the fresh fat or the oxidized fat treated at 50 degrees C,
irrespective of the dietary vitamin E concentration. However, in Experiment 2,
the composition of LDL apolipoproteins and uptake of LDL by macrophages were not
different between rats fed the fresh fat diet and those fed the oxidized fat
diet. We conclude that ingestion of oxidized fats does not adversely affect the
lipoprotein profile in the rat model used, and does not cause modifications of
apolipoproteins that would lead to enhanced uptake of LDL via macrophage
scavenger receptors.
PMID: 12949373 [PubMed]
160: J Nutr Biochem. 2003 Aug;14(8):480-6.
Beneficial effects of a diet rich in a mixture of n - 6/n - 3 essential fatty
acids and of their metabolites on cyclosporine - nephrotoxicity.
Tsipas G, Morphake P.
Laboratory of Zoology, Biochemistry and Molecular Biology. Department of
Environmental and Natural Resources. Management School of Natural Resources and
Enterprises Management. University of Ioannina, 301.00, Agrinio, Greece.
gtsipas@cc.uoi.gr
In this study we investigated the role of a mixture of n-6/n-3 essential fatty
acids, in the cyclosporine model nephrotoxicity.Administration of cyclosporine
in rats decreased creatinine clearance and provoked body weight loss, but it did
not induce proteinuria and did not alter the urine volume. These changes were
associated with decreased urinary ratios of prostaglandin E/thromboxane B and
prostaglandin I/thromboxane B excretions. Light microscopic sections showed that
100% of the animals were affected by histological tubular lesions on their
kidneys.Administration of cyclosporine to animals fed for 3 months on standard
chow containing a mixture of n - 6/n - 3 essential fatty acids, restored
creatinine clearance, augmented urine volume and prevented body weight loss. The
improvement of renal function was accompanied by increased urinary ratios of
prostaglandin E/thromboxane B and prostaglandin I/thromboxane B excretions.
Light microscopic sections showed that only 40% of the animals demonstrated
histological tubular lesions, of minor importance, to their kidneys.Our results
suggest that the metabolites of arachidonic acid can play important role in the
development of cyclosporine-nephrotoxicity because they increase the levels of
thromboxane A and that the enchanced synthesis of prostaglandins (E) and (I)
induced by a mixture of n - 6/n - 3 essential fatty acids, could play a
beneficial role in the prevention of this renal dysfunction.
PMID: 12948879 [PubMed]
161: Diabetes. 2003 Sep;52(9):2205-12.
Effect of exercise intensity on skeletal muscle AMPK signaling in humans.
Chen ZP, Stephens TJ, Murthy S, Canny BJ, Hargreaves M, Witters LA, Kemp BE,
McConell GK.
St. Vincent's Institute of Medical Research, University of Melbourne, Fitzroy,
Victoria, Australia.
The effect of exercise intensity on skeletal muscle AMP-activated protein kinase
(AMPK) signaling and substrate metabolism was examined in eight men cycling for
20 min at each of three sequential intensities: low (40 +/- 2% VO(2) peak),
medium (59 +/- 1% VO(2) peak), and high (79 +/- 1% VO(2) peak). Muscle free
AMP/ATP ratio only increased at the two higher exercise intensities (P < 0.05).
AMPK alpha 1 (1.5-fold) and AMPK alpha 2 (5-fold) activities increased from low
to medium intensity, with AMPK alpha 2 activity increasing further from medium
to high intensity. The upstream AMPK kinase activity was substantial at rest and
only increased 50% with exercise, indicating that, initially, signaling through
AMPK did not require AMPK kinase posttranslational modification. Acetyl-CoA
carboxylase (ACC)-beta phosphorylation was sensitive to exercise, increasing
threefold from rest to low intensity, whereas neuronal NO synthase (nNOS) micro
phosphorylation was only observed at the higher exercise intensities. Glucose
disappearance (tracer) did not increase from rest to low intensity, but
increased sequentially from low to medium to high intensity. Calculated fat
oxidation increased from rest to low intensity in parallel with ACC beta
phosphorylation, then declined during high intensity. These results indicate
that ACC beta phosphorylation is especially sensitive to exercise and tightly
coupled to AMPK signaling and that AMPK activation does not depend on AMPK
kinase activation during exercise.
PMID: 12941758 [PubMed]
162: J Biol Chem. 2003 Nov 7;278(45):44657-66. Epub 2003 Aug 25.
A reduction in intestinal cell pHi due to loss of the Caenorhabditis elegans
Na+/H+ exchanger NHX-2 increases life span.
Nehrke K.
Gastroenterology Unit, Department of Medicine, University of Rochester Medical
Center, Rochester, New York 14642, USA. keith_nehrke@urmc.rochester.edu
Na+/H+ exchangers are involved in cell volume regulation, fluid secretion and
absorption, and pH homeostasis. NHX-2 is a Caenorhabditis elegans Na+/H+
exchanger expressed exclusively at the apical membrane of intestinal epithelial
cells. The inactivation of various intestinal nutrient transport proteins has
been shown previously to influence aging via metabolic potential and a mechanism
resembling caloric restriction. We report here a functional coupling of NHX-2
activity with nutrient uptake that results in long lived worms. Gene
inactivation of nhx-2 by RNAi led to a loss of fat stores in the intestine and a
40% increase in longevity. The NHX-2 protein was coincidentally expressed with
OPT-2, an oligopeptide transporter that is driven by a transmembrane proton
gradient and that is also known to be involved in fat accumulation. Gene
inactivation of opt-2 led to a phenotype resembling that of nhx-2, although not
as severe. In order to explore this potential functional interaction, we
combined RNA interference with a genetically encoded, fluorescence-based reagent
to measure intestinal intracellular pH (pHi) in live worms under physiological
conditions. Our results suggest first that OPT-2 is the main dipeptide uptake
pathway in the nematode intestine, and second that dipeptide uptake results in
intestinal cell acidification, and finally that recovery following
dipeptide-induced acidification is normally a function of NHX-2. The loss of
NHX-2 protein results in decreased steady-state intestinal cell pHi, and we
hypothesize that this change perturbs proton-coupled nutrient uptake processes
such as performed by OPT-2. Our data demonstrate a functional role for a Na+/H+
exchanger in nutrient absorption in vivo and lays the groundwork for examining
integrated acid-base physiology in a non-mammalian model organism.
PMID: 12939266 [PubMed]
163: J Med. 2002;33(1-4):247-64.
Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: an
overview.
Preuss HG, DiFerdinando D, Bagchi M, Bagchi D.
Department of Physiology, Medicine and Pathology, Georgetown University Medical
Center, Washington, DC 20057, USA. preusshg@georgetown.edu
Obesity is a serious health problem throughout the world. More than half of U.S.
adults are overweight (61%) and more than a quarter (26%) of U.S. adults are
obese. The inability of many individuals to keep their weight in check by diet
and exercise has created a need for additional therapeutic means to combat
obesity. Despite great effort, the pharmaceutical industry has not come up with
the solution; because most weight-loss drugs to date have serious adverse
effects to health and well-being. The theory that beta agonists, especially beta
3 agonists, can affect body weight and fat mass is well accepted. Ephedrine has
proven time and time again that it is an effective weight loss agent through its
ability to increase thermogenesis and quench appetite. However, the publicity
concerning adverse reactions has led to its gradual withdrawal from use by many
despite the perceived consequences of obesity. Many companies are now
substituting Citrus aurantium for ephedra in their formulations. Citrus
aurantium, an agent containing beta agonists, has been reported to aid in weight
loss in two studies and increase thermogenesis, at least to some extent, in
three studies. Colker et al. (1999) reported that in a double-blind,
placebo-controlled, randomized study the subjects receiving a combination of
Citrus aurantium, caffeine and St John's Wort, lost significant amounts of total
body weight while on a strict diet and exercise. Those in the placebo and
control groups who also were on the same restricted diet did not. However,
intergroup analysis showed no statistical significance among the weight changes
in the three groups. In contrast, the loss of fat mass in the test group was
significantly greater compared to the placebo and control groups. Jones
describes an open labeled study performed on 9 women. The subjects showed a mean
of 0.94 kg lost during the first week when no product was given and 2.40 kg
during the second week when a Citrus aurantium product was taken. Body weight
losses were statistically greater during the second week compared to the first
week. Since most clinicians would agree that the most weight loss should occur
initially coinciding with a greater fluid loss during the first week, these
differences are even more remarkable. Three studies reported increased metabolic
rates when ingesting Citrus aurantium products, however, at least two of these
studies were acute. At present, Citrus aurantium may be the best thermogenic
substitute for ephedra. However, more studies are needed to establish this
definitively.
Publication Types:
Review
Review, Tutorial
PMID: 12939122 [PubMed]
164: Am J Pathol. 2003 Sep;163(3):1201-13.
Induction of fatal inflammation in LDL receptor and ApoA-I double-knockout mice
fed dietary fat and cholesterol.
Zabalawi M, Bhat S, Loughlin T, Thomas MJ, Alexander E, Cline M, Bullock B,
Willingham M, Sorci-Thomas MG.
Department of Pathology, Wake Forest University Health Sciences, Medical Center
Boulevard, Winston-Salem, NC 27157, USA.
Atherogenic response to dietary fat and cholesterol challenge was evaluated in
mice lacking both the LDL receptor (LDLr(-/-)) and apoA-I (apoA-I(-/-)) gene,
LDLr(-/-)/apoA-I(-/-) or double-knockout mice. Gender- and age-matched
LDLr(-/-)/apoA-I(-/-) mice were fed a diet consisting of 0.1% cholesterol and
10% palm oil for 16 weeks and compared to LDLr(-/-) mice or single-knockout
mice. The LDLr(-/-) mice showed a 6- to 7-fold increase in total plasma
cholesterol (TPC) compared to their chow-fed mice counterparts, while
LDLr(-/-)/apoA-I(-/-) mice showed only a 2- to 3-fold increase in TPC compared
to their chow-fed controls. This differential response to the atherogenic diet
was unanticipated, since chow-fed LDLr(-/-) and LDLr(-/-)/apoA-I(-/-) mice began
the study with similar LDL levels and differed primarily in their HDL
concentration. The 6-fold diet-induced increase in TPC observed in the LDLr(-/-)
mice occurred mainly in VLDL/LDL and not in HDL. Mid-study plasma samples taken
after 8 weeks of diet feeding showed that LDLr(-/-) mice had TPC concentrations
approximately 60% of their 16-week level, while the LDLr(-/-)/apoA-I(-/-) mice
had reached 100% of their 16-week TPC concentration after only 8 weeks of diet.
Male LDLr(-/-) mice showed similar aortic cholesterol levels to male
LDLr(-/-)/apoA-I(-/-) mice despite a 4-fold higher VLDL/LDL concentration in the
LDLr(-/-) mice. A direct comparison of the severity of aortic atherosclerosis
between female LDLr(-/-) and LDLr(-/-)/apoA-I(-/-) mice was compromised due to
the loss of female LDLr(-/-)/apoA-I(-/-) mice between 10 and 14 weeks into the
study. Diet-fed female and, with time, male LDLr(-/-)/apoA-I(-/-) mice suffered
from severe ulcerated cutaneous xanthomatosis. This condition, combined with a
complete depletion of adrenal cholesterol, manifested in fatal wasting of the
affected mice. In conclusion, LDLr(-/-) and LDLr(-/-)/apoA-I(-/-) mice showed
dramatic TPC differences in response to dietary fat and cholesterol challenge,
while despite these differences both genotypes accumulated similar levels of
aortic cholesterol.
PMID: 12937162 [PubMed]
165: Obes Surg. 2003 Aug;13(4):615-21.
Insulin resistance, leptin and TNF-alpha system in morbidly obese women after
gastric bypass.
Molina A, Vendrell J, Gutierrez C, Simon I, Masdevall C, Soler J, Gomez JM.
Department of Endocrinology, Princeps d'Espanya Hospital, Barcelona, Spain.
30903xrc@comb.es
Obesity is a complex disease associated with insulin resistance. Leptin and the
TNF-alpha system could be involved in the pathogenesis of obesity and insulin
resistance. Gastric bypass (GBP) is a surgical treatment for morbidly obese
patients. We conducted a study after GBP to analyze the pattern of variation of
anthropometric and body composition variables, leptin and sTNFR1 and 2. METHODS:
29 morbidly obese women were studied, at baseline and throughout 6 months after
gastric bypass. RESULTS: At baseline, the BMI was 49 +/- 6 kg/m(2) and patients
showed a higher fasting insulin resistance index (FIRI), leptin, leptin/fat mass
and sTNFR1 and 2 than did controls. 6 months after GBP, BMI was 35+/-4, and
FIRI, leptin and leptin/fat mass decreased significantly in the first months and
throughout the follow-up. sTNFR1 and 2 showed an initial increase, but at 6
months their concentrations were similar to baseline (2.6+/-0.8 vs 3.1+/-0.95
ng/ml, P < 0.05; 4.6+/-1.4 vs 7+/-2.5 ng/ml, P < 0.05). At baseline, there was
no correlation between leptin and BMI and body composition variables but there
was a correlation with fat mass (r=0.42, P=0.004) and sTNFR1 (r=0.58, P=0.001).
At 6 months, there was a correlation between leptin and BMI (r=0.53, P=0.004)
and sTNFR1 (r=0.46, P=0.013). CONCLUSIONS: Morbidly obese women after GBP became
less insulin resistant with lower leptin concentrations, but showed an initial
increase of sTNFR1 and 2. This pattern of variation of the leptin TNF-alpha axis
suggests a disregulation of the system after dramatic weight loss and also that
insulin and leptin up-regulate TNF-alpha production irrespective of insulin
resistance status.
PMID: 12935365 [PubMed]
166: Endocrinology. 2003 Sep;144(9):3950-7.
Evidence that sensitivity to growth hormone (GH) is growth period and tissue
type dependent: studies in GH-deficient lit/lit mice.
Kasukawa Y, Baylink DJ, Guo R, Mohan S.
Musculoskeletal Disease Center, Jerry L. Pettis Veterans Affairs Medical Center,
Loma Linda, California 92357, USA.
We previously found that the magnitude of skeletal deficits caused by GH
deficiency varied during different growth periods. To test the hypothesis that
the sensitivity to GH is growth period dependent, we treated GH-deficient
lit/lit mice with GH (4 mg/kg body weight.d) or vehicle during the prepubertal
and pubertal (d 7-34), pubertal (d 23-34), postpubertal (d 42-55), and adult (d
204-217) periods and evaluated GH effects on the musculoskeletal system by dual
energy x-ray absorptiometry (DEXA) and peripheral quantitative computed
tomography. GH treatment during different periods significantly increased total
body bone mineral content, bone mineral density (BMD), bone area, and lean body
mass and decreased percentage of fat compared with vehicle; however, the
magnitude of change varied markedly depending on the treatment period. For
example, the increase in total body BMD was significantly (P < 0.01) greater
when GH was administered between d 42-55 (15%) compared with pubertal (8%) or
adult (7.7%) periods, whereas the net loss in percentage of body fat was
greatest (-56%) when GH was administered between d 204 and 216 and least (-27%)
when GH was administered between d 7 and 35. To determine whether GH-induced
anabolic effects on the musculoskeletal system are maintained after GH
withdrawal, we performed DEXA measurements 3-7 wk after stopping GH treatment.
The increases in total body bone mineral content, BMD, and lean body mass, but
not the decrease in body fat, were sustained after GH withdrawal. Our findings
demonstrate that the sensitivity to GH in target tissues is growth period and
tissue type dependent and that continuous GH treatment is necessary to maintain
body fat loss but not BMD gain during a 3-7 wk follow-up.
PMID: 12933669 [PubMed]
167: Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1875-80. Epub 2003 Aug
21.
Gender differences in postprandial ketone bodies in normolipidemic subjects and
in untreated patients with familial combined hyperlipidemia.
Halkes CJ, van Dijk H, Verseyden C, de Jaegere PP, Plokker HW, Meijssen S,
Erkelens DW, Cabezas MC.
Department of Vascular Medicine, University Medical Center Utrecht, The
Netherlands.
OBJECTIVE: An increased hepatic flow of free fatty acids (FFAs) is associated
with impaired peripheral FFA trapping by malfunctioning of the complement
component 3 (C3)/acylation-stimulating protein system and overproduction of VLDL
in familial combined hyperlipidemia (FCHL). Postprandial ketone bodies reflect
FFA oxidation in the liver, but the postprandial changes in male and female
patients separately have not been determined yet. Gender differences in
postprandial ketone bodies and C3 changes were investigated in normolipidemic
patients and patients with untreated FCHL. METHODS AND RESULTS: Thirty-two
normolipidemic patients (16 female and 16 male) and 19 patients with untreated
normolipidemia (9 female and 10 male) underwent an oral fat-loading test. Total
and incremental areas under the curves (AUC and dAUC, respectively) after the
oral fat load were calculated. Triglyceride AUC was similar between genders in
each group. Normolipidemic female subjects showed a higher levels of
dAUC-hydroxybutyric acid than male subjects (1.37+/-0.49 and 0.98+/-0.43 mmol x
h/L). In FCHL, a similar trend was observed in female (1.92+/-0.38) compared
with male (1.55+/-0.87) subjects. In contrast to normolipidemia, FCHL did not
show a postprandial increase in C3, although C3 was higher in FCHL. CONCLUSIONS:
Women have higher postprandial ketone bodies than men, probably reflecting
enhanced postprandial hepatic FFA oxidation. In FCHL, both genders have higher
postprandial ketone bodies and therefore higher hepatic FFA delivery. The higher
fasting and postprandial C3 levels in FCHL may reflect resistance of the
C3/acylation-stimulating protein system to promote peripheral fatty acid
trapping.
PMID: 12933534 [PubMed]
168: Nutr Metab Cardiovasc Dis. 2003 Apr;13(2):80-6.
Dietary L-aspartate and L-glutamate inhibit fatty streak initiation in
cholesterol-fed rabbit.
Yanni AE, Yatzidis HA, Kavantzas NG, Agapitos EV, Perrea DN, Karayannacos PE.
Laboratory of Experimental Surgery and Surgical Research, Medical School,
National and Kapodistrian University of Athens, Athens, Greece. ayanni@hua.gr
BACKGROUND AND AIM: Low-density lipoprotein (LDL) oxidation is a potential
atherogenic agent, and protecting LDL from oxidation prevents atherogenesis. It
has been shown that L-aspartate and L-glutamate decrease lipid peroxidation
after reoxygenation by means of the initiation of the cardiopulmonary bypass
circuit (CPB), when supplemented to the CPB prime, and so they may protect
against atherogenesis. The aim of this study was to evaluate the effect of the
dietary administration of L-aspartate and L-glutamate on fatty streak onset in
cholesterol-fed rabbit. METHODS AND RESULTS: Male New Zealand white rabbits were
fed for four weeks with either a high-cholesterol plus corn oil diet (control
group) or the same diet supplemented with 12.5 mM L-aspartate and 12.5 mM
L-glutamate in drinking water (Asp + Glu group). The mononuclear cells adhering
to the endothelium and the intimal foam cells of the thoracic aorta were used to
quantify the extent of atherosclerosis. Total serum cholesterol and lipid
peroxidation activity, measured as thiobarbituric acid reactive substances
(TBARS), were determined 0, 1 and 4 weeks after a 2-week adaptation period.
There were no between-group differences in body weight or food intake during the
intervention. Serum TBARS were significantly increased in both groups during the
experimental period but without any statistical difference between groups. At
the end of the dietary intervention, there was a ten-fold increase in total
serum cholesterol concentration in both groups vs baseline. The numbers of
adherent mononuclear cells and intimal foam cells were both significantly lower
in the Asp + Glu group. CONCLUSIONS: Our results suggest that dietary
supplementation with L-aspartate and L-glutamate seems to protect the arterial
wall from atherogenesis in an experimental animal.
PMID: 12929620 [PubMed]
169: J Lipid Res. 2003 Dec;44(12):2234-41. Epub 2003 Aug 16.
Efficacy and safety of dietary supplements containing CLA for the treatment of
obesity: evidence from animal and human studies.
Larsen TM, Toubro S, Astrup A.
Department of Human Nutrition, Center for Advanced Food Studies, The Royal
Veterinary and Agricultural University, DK-1958 Frederiksberg C, Denmark.
tml@kvl.dk
Dietary supplements containing conjugated linoleic acid (CLA) are widely
promoted as weight loss agents available over the counter and via the Internet.
In this review, we evaluate the efficacy and safety of CLA supplementation based
on peer-reviewed published results from randomized, placebo-controlled, human
intervention trials lasting more than 4 weeks. We also review findings from
experimental studies in animals and studies performed in vitro. CLA appears to
produce loss of fat mass and increase of lean tissue mass in rodents, but the
results from 13 randomized, controlled, short-term (<6 months) trials in humans
find little evidence to support that CLA reduces body weight or promotes
repartitioning of body fat and fat-free mass in man. However, there is
increasing evidence from mice and human studies that the CLA isomer trans-10,
cis-12 may produce liver hypertrophy and insulin resistance via a redistribution
of fat deposition that resembles lipodystrophy. CLA also decreases the fat
content of both human and bovine milk. In conclusion, although CLA appears to
attenuate increases in body weight and body fat in several animal models, CLA
isomers sold as dietary supplements are not effective as weight loss agents in
humans and may actually have adverse effects on human health.
PMID: 12923219 [PubMed]
170: Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10207-12. Epub 2003 Aug 14.
Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes
induced by high-fat/high-carbohydrate diets.
Abu-Elheiga L, Oh W, Kordari P, Wakil SJ.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor
College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Malonyl-CoA, generated by acetyl-CoA carboxylases ACC1 and ACC2, is a key
metabolite in the control of fatty acid synthesis and oxidation in response to
dietary changes. ACC2 is associated to the mitochondria, and Acc2-/- mice have a
normal lifespan and higher fatty acid oxidation rate and accumulate less fat.
Mutant mice fed high-fat/high-carbohydrate diets weighed less than their WT
cohorts, accumulated less fat, and maintained normal levels of insulin and
glucose, whereas the WT mice became type-2 diabetic with hyperglycemic and
hyperinsulinemic status. Fatty acid oxidation rates in the soleus muscle and in
hepatocytes of Acc2-/- mice were significantly higher than those of WT cohorts
and were not affected by the addition of insulin. mRNA levels of uncoupling
proteins (UCPs) were significantly higher in adipose, heart (UCP2), and muscle
(UCP3) tissues of mutant mice compared with those of the WT. The increase in the
UCP levels along with increased fatty acid oxidation may play an essential role
in the regulation of energy expenditure. Lowering intracellular fatty acid
accumulation in the mutant relative to that of the WT mice may thus impact
glucose transport by higher GLUT4 activity and insulin sensitivity. These
results suggest that ACC2 plays an essential role in controlling fatty acid
oxidation and is a potential target in therapy against obesity and related
diseases.
PMID: 12920182 [PubMed]
171: J Am Geriatr Soc. 2003 Sep;51(9):1237-43.
Insulin-like growth factor-1 and interleukin 6 predict sarcopenia in very old
community-living men and women: the Framingham Heart Study.
Payette H, Roubenoff R, Jacques PF, Dinarello CA, Wilson PW, Abad LW, Harris T.
Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Tufts University,
Boston, Massachusetts, USA. helene.payette@usherbrooke.ca
OBJECTIVES: To assess the prognostic role of the inflammatory cytokine,
interleukin 6 (IL-6), and insulin-like growth factor-1 (IGF-1) in predicting
2-year changes in fat-free mass (FFM) while controlling for potential
confounders. DESIGN: Population-based cohort, the Framingham Heart Study,
examined in 1992-93 and 1994-95. SETTING: General community. PARTICIPANTS: Two
hundred thirty-two men and 326 women aged 72 to 92. MEASUREMENTS: IGF-1 was
measured using radio-immunoassay and cellular IL-6 production using
non-cross-reacting radioimmunoassays. FFM was estimated using
population-specific equations for predicting FFM from bioelectrical impedance
analysis developed separately for men and women. RESULTS: Higher IGF-1 predicted
smaller loss of FFM in men than lower IGF-1 did (P=.002), after adjusting for
age, baseline FFM, fat mass, and 2-year weight changes, whereas cellular IL-6
was a significant predictor of sarcopenia in women (P=.02). Weight change was a
strong determinant of change in FFM in both sexes (P<.0001). CONCLUSION:
Predictors of sarcopenia include body composition characteristics that are
common to men and women and sex-specific metabolic predictors. Sarcopenia
appears to reflect a withdrawal of anabolic stimuli, such as growth hormone, in
men but an increase in catabolic stimuli, such as cellular IL-6, in women.
PMID: 12919235 [PubMed]
172: J Dairy Sci. 2003 Jul;86(7):2352-8.
Effect of omitting one milking weekly on lactational performances and
morphological udder changes in dairy cows.
Ayadi M, Caja G, Such X, Knight CH.
Unitat de Produccio Animal, Department of Animal and Food Sciences, Universitat
Autonoma de Barcelona, 08193 Bellaterra, Spain.
The response of dairy cows to omitting one milking weekly was investigated in
two successive experiments conducted with Holstein cows milked twice daily.
Experiment 1 compared the lactational performances and udder changes in eight
cows (31.2 L/d, 201 d in milk) in the 5 wk before and the 5 wk after introducing
the suppression of one milking weekly. Milk yield was recorded daily and milk
composition twice weekly. Milk partitioning in the udder (alveolar and cisternal
milk) and cisternal size (ultrasonography), 8 h after milking, were also
measured at the start and the end of the experiment. Although daily milk yield
decreased 32% during the experiment (10 wk), linear regression analysis revealed
a loss of milk yield of 1.1 L/d (3.7%) as a consequence of the omission of one
milking weekly. Milk composition, lactation persistency, and somatic cell count
(SCC) were unaffected by milking omission. Milk partitioning in the udder
decreased by 38% in alveolar milk volume and showed a tendency to decrease in
cisternal milk volume (15%) and cisternal size (7%), as a result of milking
omission and advancing lactation. Loss in total milk yield was negatively
related with cisternal milk volume (r = -0.77) and cisternal size (r = -0.70)
indicating smaller losses in the udders with large cisterns. In Experiment 2,
five cows (21.0 L/d, 227 d in milk) previously adapted to the milking omission
schedule were used to study the daily effects of milking omission on milk yield,
milk composition and udder health during 10 wk. Milk yield and milk composition
were approximately constant but SCC increased with lactation stage. The omission
of one milking caused an important decrease in milk yield, fat content and SCC
on the omission day and a compensatory increase over the following 2 d, but milk
protein and lactose did not vary. All variables reached the average weekly value
three days after the milking omission (six milkings). In conclusion, under the
conditions used, omitting one milking weekly slightly reduced milk yield and did
not affect milk composition when healthy cows were used. Milk losses by milking
omission depend on udder cistern characteristics; evaluating cistern size by
ultrasonography may be a useful tool for choosing cows that are better adapted
to a reduced milking frequency.
PMID: 12906052 [PubMed]
173: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2000 Jun;22(3):269-72.
[Effect of weight loss on adipose tissue distribution and insulin sensitivity]
[Article in Chinese]
Zhao W, Vague P, Darmon P, Janand-Delenne B.
Department of Endocrinology, PUMC Hospital, CAMS, PUMC, Beijing 100730, China.
zhaowg@public2.bta.net.cn
OBJECTIVE: To discuss the effect of weight reduction on fat distribution and
parameters of insulin sensitivity. METHODS: 12 Caucasian women with simple
obesity, aged 21 to 65 years, were treated by low caloric and high protein diet
for four weeks. A series of examinations were taken before and after the treat,
using computerized tomography for visceral and subcutaneous fat, using
euglycemic insulin clamp for parameters of insulin sensitivity. RESULTS: Weight
loss was (6 +/- 2) kg (2-11 kg). body mass index (BMI), waist, total fat,
visceral fat, and subcutaneous fat reduced significantly. However waist-hip
rate, visceral-total fat rate, and subcutaneous-total fat rate did not change
significantly. Fasting serum insulin, and fasting insulin-glucose rate decreased
significantly. Insulin metabolic clearance rate and, insulin sensitive index
increased significantly. Fasting peptide C did not change significantly.
CONCLUSIONS: The low caloric and high protein diet can reduce visceral and
subcutaneous fat. Weight loss can improve insulin sensitivity and increase
insulin metabolic clearance rate.
PMID: 12903475 [PubMed]
174: Metabolism. 2003 Aug;52(8):964-9.
Synergistic effects of testosterone and growth hormone on protein metabolism and
body composition in prepubertal boys.
Mauras N, Rini A, Welch S, Sager B, Murphy SP.
Nemours Children's Clinic Division of Endocrinology and Nemours Research
Program, Jacksonville, FL 32207, USA.
During human puberty there is a substantial increase in growth hormone (GH) and
sex steroidal hormone concentrations, as well as in GH production rates and
insulin-like growth factor-I (IGF-I) These studies were designed to investigate
some of the interactions of testosterone (T) and GH in the metabolic changes of
puberty. Ten boys with severe GH deficiency (GHD) were studied (mean age, 12.5
+/- 0.5 years) using stable isotope infusions, indirect calorimetry, and body
composition analysis. After the baseline study, they received 2 doses of T
enanthate (50 to 75 mg, intramuscular [IM]), and they were studied again 4 weeks
later. The boys were then begun on daily subcutaneous (SC) GH (0.3 mg/kg/wk),
while T therapy was continued for another 4 weeks and the studies repeated a
third time. The treatment order was randomized. Protein oxidation rates
decreased after T alone (-28%, P <.01), decreasing further after combined T/GH
treatment (-36% v baseline, P <.01). The nonoxidative leucine disposal (NOLD), a
measure of whole body protein synthesis, increased significantly after combined
T/GH regardless of treatment order. The combination of T/GH also resulted in
greater changes in body composition than T alone, with comparable decreases in
%FM and corresponding increases in fat free mass (FFM). Measures of carbohydrate
(CHO) metabolism, including glucose production and oxidation rates, were
unaffected by either T or T/GH combination. Plasma IGF-I concentrations
increased after T treatment and even more after T/GH combination, regardless of
the treatment order. In conclusion GH and T are synergistic on whole body
protein anabolism and body composition in males, even at a young age, but the
positive effects of T on protein anabolism and body composition appear to need a
basal amount of GH for those effects to be observed. GH and T both potentiate
the development of the full body composition and metabolic changes of puberty.
Publication Types:
Clinical Trial
PMID: 12898459 [PubMed]
175: J Pediatr Surg. 2003 Aug;38(8):1182-7.
Comment in:
Gastroenterology. 2004 Mar;126(3):920-1; discussion 921.
Low-fat diet impairs postresection intestinal adaptation in a rat model of short
bowel syndrome.
Sukhotnik I, Shiloni E, Krausz MM, Yakirevich E, Sabo E, Mogilner J, Coran AG,
Harmon CM.
Department of Surgery, Rappaport Faculty of Medicine, Technion, Carmel Medical
Center, Haifa, Israel.
BACKGROUND: Low-fat diets (LFD) are utilized frequently in patients with short
bowel syndrome (SBS). The purpose of this study was to investigate the effects
of LFD on intestinal adaptation, enterocyte proliferation, and enterocyte cell
death in a rat model of SBS. METHODS: Adult male Sprague-Dawley rats were
divided into 3 experimental groups: Sham-NC rats underwent bowel transection and
reanastomosis and were fed normal chow (NC), SBS-NC rats underwent 75% small
bowel resection and were fed NC, and SBS-rats were fed a low-fat diet (SBS-LFD).
Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte
apoptosis were determined on day 14 after operation. RESULTS: SBS-NC rats showed
a significant increase (v Sham-NC) in jejunal and ileal bowel and mucosal
weight, mucosal DNA and protein, villus height, and crypt depth. A significant
67% increase in crypt cell proliferation rate and 265% increase in villus
enterocyte apoptosis was seen in the ileum of SBS-NC rats compared with control
animals (P <.05). SBS-LFD animals showed lower ileal mucosal weight (29%; P
<.05), jejunal crypt depth (20%; P <.05), and ileal villus height (21%; P <.05).
A significant decrease in villus apoptosis in jejunum (74%; P <.05) and ileum
(67%; P <.05) and a decrease in cell proliferation in ileum (35%; P <.05) was
seen also after exposure to LFD compared with SBS-NC. CONCLUSIONS: In a rat
model of SBS, early LFD appears to inhibit parameters of intestinal adaptation.
A possible mechanisms for this effect may be decreased cell proliferation.
Decreased enterocyte loss via apoptosis, found in this study, may reflect a
reduced number of enterocyte.
PMID: 12891489 [PubMed]
176: Eat Weight Disord. 2003 Jun;8(2):107-13.
Three-week integrated body weight reduction programme markedly improves
performance and work capacity in severely obese patients.
Sartorio A, Ottolini S, Agosti F, Massarini M, Lafortuna CL.
Laboratorio Sperimentale di Ricerche Endocrinologiche, Istituto Auxologico
Italiano, IRCCS, Milan, Italy. sartorio@auxologico.it
The aim of this study was to assess the effects on performance and work capacity
of a short-term (3-week) integrated body weight reduction programme consisting
of an energy-restricted diet, nutritional education, psychological counselling
and aerobic exercise training at a constant metabolic load (5 days/week) in 71
severely obese patients (18 males and 53 females aged 29.3 +/- 0.8 years, with a
mean weight of 113.8 +/- 2.2 kg and a mean BMI of 41.3 +/- 0.5 kg/m(-2)). Body
mass and composition, and maximum oxygen consumption (VO2max) were determined
before and after the programme. The caloric equivalent of work output and a
performance index (PI) during 10 min of bicycle ergometer pedalling (50-60 rpm)
and 20 min of treadmill walking (incline 0-3%) at a constant metabolic load (50%
of individual VO2max during the preliminary conditioning period--1st week--and
60% during the exercise conditioning period--2nd and 3rd week) were evaluated
daily throughout the study. After the programme, body mass reduced significantly
(-4.5%, p<0.001), the weight loss being sustained entirely by a significant
reduction in fat mass (-7.6%, p<0.001) without any significant changes in
fat-free mass. Absolute and body mass-related VO2max significantly increased by
respectively 14.5% and 20.2% (p<0.001). Both daily work output during constant
metabolic load (ANOVA, p<0.05-0.001) and PI (ANOVA, p<0.05-0.001) increased
significantly during each week of the programme, leading to a total increase in
work output in response to exercise conditioning of 44.6 +/- 5.8 kcal. It is
concluded that the changes in exercise capacity induced by the present programme
offer significant advantages for obese patients that can be quantified in terms
of an improvement in their ability to perform everyday activities, thus
contributing towards improving their quality of life.
PMID: 12880187 [PubMed]
177: J Thromb Haemost. 2003 Mar;1(3):566-72.
Pro- and antioxidant activities of docosahexaenoic acid on human blood
platelets.
Vericel E, Polette A, Bacot S, Calzada C, Lagarde M.
UMR 585 INSERM/INSA Lyon, Villeurbanne, France. Evelyne.Vericel@insa-lyon.fr
n - 3 polyunsaturated fatty acids may protect against vascular diseases,
however, their high accumulation in membranes may increase lipid peroxidation
and subsequently induce deleterious effects in patients suffering from oxidative
stress. This led us to investigate in vitro the dose-dependent effect of
docosahexaenoic acid (DHA) on the redox status of human platelets. We have
compared the effect of different DHA concentrations (0.5, 5 and 50 micro mol
L(-1)) corresponding to DHA/albumin ratios of 0.01, 0.1 and 1. At the highest
concentration, DHA elicited a marked oxidative stress, as evidenced by high
malondialdehyde and low vitamin E levels whereas the lowest DHA concentration
significantly decreased the malondialdehyde formation, with no change in vitamin
E. The proportion of DHA was only increased in plasmalogen
phosphatidylethanolamine at low concentration to rise in all
phosphatidyl-choline and -ethanolamine subclasses at high concentration. Thus,
the results show a biphasic effect of DHA with antioxidant and prooxidant
effects at low and high concentrations, respectively, with a possible
relationship with the phospholipid subclass in which it accumulates.
PMID: 12871467 [PubMed]
178: J Gerontol A Biol Sci Med Sci. 2003 Jul;58(7):618-25.
Oral testosterone supplementation increases muscle and decreases fat mass in
healthy elderly males with low-normal gonadal status.
Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE.
Department of Medicine, University of Adelaide, Royal Adelaide Hospital,
Australia. gary.wittert@adelaide.edu.au
BACKGROUND: Loss of muscle mass (sarcopenia) leads to frailty in older men. The
decline in testosterone over the life span may contribute to this muscle loss.
We studied the ability of oral testosterone to prevent muscle loss in older men
over a 12-month period. METHODS: A standard dose (80 mg twice daily) of
testosterone undecanoate or placebo was administered for 1 year to 76 healthy
men aged 60 years or older. All men had a free testosterone index of 0.3-0.5,
which represents a value below the normal lower limit for young men (19-30
years), but remains within the overall normal male range. Measurements of body
composition, muscle strength, hormones, and safety parameters were obtained at
0, 6, and 12 months. RESULTS: Lean body mass increased (p =.0001) and fat mass
decreased (p =.02) in the testosterone as compared with the placebo-treated
group. There were no significant effects on muscle strength. There was a
significant increase in hematocrit (0.02%) in the testosterone-treated group (p
=.03). Plasma triglycerides, total cholesterol, and low-density lipoprotein
cholesterol levels were similar in both groups, but there was a decrease in
high-density lipoprotein cholesterol (-0.1 mmol/L) at 12 months in the
testosterone group as compared to the placebo group (p = 0.026). There were no
differences in prostate-specific antigen or systolic or diastolic blood pressure
between the groups. CONCLUSION: Oral testosterone administration to older
relatively hypogonadal men results in an increase in muscle mass and a decrease
in body fat.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12865477 [PubMed]
179: Acta Physiol Scand. 2003 Aug;178(4):443-52.
Regulatory mechanisms in the interaction between carbohydrate and lipid
oxidation during exercise.
Spriet LL, Watt MJ.
Department of Human Biology and Nutritional Sciences, University of Guelph,
Guelph, Ontario, Canada.
At the onset of exercise, signals from inside and outside the muscle cell
increase the availability of carbohydrate (CHO) and fat to provide the fuel
required for ATP production. CHO and fat oxidation are the dominant sources of
aerobic ATP production and both pathways must be heavily upregulated during
exercise to meet the increased energy demand. Within this paradigm, there is
room for shifts between the proportion of energy that is provided from CHO and
fat. It has long been known that increasing the availability of endogenous or
exogenous CHO can increase the oxidation of CHO and decrease the oxidation of
fat. The opposite is also true. While descriptive studies documenting these
changes are numerous, the mechanisms regulating these shifts in fuel use in the
face of constant energy demand have not been thoroughly elucidated. It would be
expected, for example, that any fat-induced shift in CHO metabolism would target
the enzymes that play key roles in regulating CHO metabolism and oxidation.
Inside the muscle these could include glucose uptake (GLUT4) and phosphorylation
(hexokinase), glycogenolysis (glycogen phosphorylase), glycolysis
(phosphofructokinase) and conversion to acetyl CoA (pyruvate dehydrogenase). The
same would be expected for a CHO-induced down regulation of fat metabolism and
oxidation and might target transport of long chain fatty acids into the cell
(fatty acid translocase CD36), release of fatty acids from intramuscular
triacylglycerol (hormone sensitive lipase) and transport into the mitochondria
(carnitine palmitoyl transferase complex). This review summarizes the work
describing the interaction between CHO and fat metabolism in human skeletal
muscle during exercise and presents the theories that may account for CHO/fat
interaction during exercise.
Publication Types:
Review
Review, Tutorial
PMID: 12864750 [PubMed]
180: An Sist Sanit Navar. 2002;25 Suppl 1:7-16.
[Obesity: concept, classification and diagnosis]
[Article in Spanish]
Barbany M, Foz M.
Secretaria de la Sociedad Espanola para el Estudio de la Obesidad, C/ Barcelona,
7-9, 08301 Mataro, Barcelona. 22108mbc@comb.es
Obesity is a chronic disease that is characterised by an increase of fat mass
and as a result by an increase in weight. There is therefore an increase in the
energy reserves of the organism in the form of fat. The term chronic is applied
due to its forming part of the group of diseases that we are unable to cure with
the therapeutic arsenal that is now available. From an anthropometric point of
view, which is habitually used in the clinic, a person is considered to be obese
with a Body Mass Index equal to or higher than 30 kg/m2. To be able to evaluate
obesity account must be taken not only of the anthropometric aspects but also of
the possible genetic factors; the causes of the disease must be studied and the
possible existence of associated complications and diseases must be checked.
Treatment must always be personalised and adapted to the characteristics and
comorbidities presented by the patient. The dominant criteria favourable to
therapeutic intervention in obesity are especially based on the demonstration
that with a moderate loss of body weight (5-10 %) a notable improvement can be
obtained in the comorbidity associated with obesity and in the quality of life
of the obese patient.
PMID: 12861266 [PubMed]
181: Diabetologia. 2003 Aug;46(8):1082-9. Epub 2003 Jul 11.
Lifestyle changes and lipid metabolism gene expression and protein content in
skeletal muscle of subjects with impaired glucose tolerance.
Mensink M, Blaak EE, Vidal H, De Bruin TW, Glatz JF, Saris WH.
Nutrition and Toxicology Research Institute Maastricht, Maastricht University,
6200 MD Maastricht, The Netherlands. m.mensink@hb.unimaas.nl
AIMS/HYPOTHESIS. Skeletal muscle of pre-diabetic patients is characterised by a
diminished capacity to handle fatty acids. A diminished content of several
enzymes involved in fatty-acid transport and oxidation have been suggested to
underlie these defects. The aim of this study was to investigate whether the
combination of dietary advice, increased physical activity and weight loss
improves lipid metabolic gene and protein expression in skeletal muscle of
subjects with impaired glucose tolerance. METHODS. Before and after 1 year of a
lifestyle-intervention programme, expression of several genes and proteins
involved in lipid metabolism were measured in vastus lateralis muscle biopsies
from subjects in the intervention ( n=7) and control group ( n=6). RESULTS.
After 1 year the intervention group had an improved glycaemic control and
reduced body fat compared to the control group. Significant differences were
observed for acetyl CoA-carboxylase 2 and uncoupling protein 2 expression (ACC2:
-16.8+/-12.4% vs +51.5+/-32.3% for the intervention and control group
respectively; p<0.05) (UCP2: -26.9+/-10.3% vs +10.5+/-6.2% for the intervention
and control group respectively; p<0.05). Change in 3-hydroxyacyl-CoA
dehydrogenase protein content tended to be different between groups (+3.2+/-1.1
vs -0.9+/-1.9 U/mg.ww for the intervention and control group, p=0.07).
CONCLUSIONS/INTERPRETATION. Lifestyle changes leading to an improved glycaemic
control and reduced adiposity, resulted in a down-regulation of ACC-2 and UCP2
expression and in an increase in HAD protein content, reflecting a better
capacity to utilise fatty acids.
PMID: 12856127 [PubMed]
182: Obes Res. 2003 Jul;11(7):880-7.
Metabolic partitioning of endogenous fatty acid in adipocytes.
Wang T, Zang Y, Ling W, Corkey BE, Guo W.
Obesity Research Center, Department of Medicine, Boston University School of
Medicine, Boston, Massachusetts 02118, USA.
OBJECTIVE: To develop an accurate new method to measure the partitioning of
adipocyte endogenous fatty acids among different metabolic pathways, a critical
step toward understanding the regulatory mechanism by which fat disposition is
modulated. RESEARCH METHODS AND PROCEDURES: Isolated primary rat adipocytes were
pre-incubated with isotope-labeled fatty acids. This allows determination of the
specific activity of labeled fatty acids in the endogenous lipid pool. After the
removal of exogenous fatty acids, the disposition of endogenous fatty acids into
the three major metabolic pathways, namely, oxidation, re-esterification, and
release into the medium, was measured independently. This was compared with the
total lipolytic release of endogenous fatty acids, as measured by glycerol
release. Adipocytes from normal fed and fasted animals were used to determine
the effects of physiological variations on the metabolic fate of endogenous
fatty acids. RESULTS: In normal fed animals, 0.2% of endogenous fatty acids were
oxidized, 50.1% were released, and 49.7% were re-esterified. Fasting doubled the
partitioning of fatty acids toward oxidation (p < 0.05) in association with
increased lipolysis (1.4-fold increase) (p < 0.05). This effect was completely
abolished by the addition of insulin to the cells (61% reduction) (p < 0.05).
DISCUSSION: The endogenous fatty acids in adipocytes are actively oxidized. This
process can be regulated by altered physiological conditions or by insulin. Over
time, it is possible that a small shift of fatty acids toward oxidation could
have a significant impact on body fuel economy. This hypothesis needs to be
tested.
PMID: 12855758 [PubMed]
183: Free Radic Biol Med. 2003 Jul 15;35(2):189-99.
Mechanisms of enhanced apoptosis in HL-60 cells by UV-irradiated n-3 and n-6
polyunsaturated fatty acids.
Arita K, Yamamoto Y, Takehara Y, Utsumi T, Kanno T, Miyaguchi C, Akiyama J,
Yoshioka T, Utsumi K.
Institute of Medical Science, Kurashiki Medical Center, Kurashiki, Japan.
We examined the effects of arachidonic acid (AA), eicosapentaenoic acid (EPA),
and their ultraviolet (UV)-irradiated products on HL-60 cells and isolated
mitochondria to explore the following four obscure points in the mechanism of
polyunsaturated fatty acids (PUFAs)-induced apoptosis: (i). the role of reactive
oxygen species, (ii). the interaction of PUFAs and their metabolites with
mitochondria in situ, (iii). the cyclosporine A (CsA)-sensitivity in
PUFA-induced membrane permeability transition, (iv). the specificity of oxidized
n-3 PUFAs in the induction of apoptosis in cancer cells. UV-oxidized PUFAs
contained conjugated dienes and thiobarbituric acid reactive substances (TBARS).
The apoptotic effects of PUFAs on HL-60 cells were increased by UV-irradiation
whereas the swelling effect of PUFAs on isolated mitochondria was decreased.
Both oxidized n-3 and n-6 PUFAs induced increased depolarization,
ferricytochrome c release, the activation of various caspases, and
DNA-fragmentation in a CsA-insensitive mechanism concomitant with a slight
increase in the value of TBARS in cells. Furthermore, there were no significant
differences in the mechanism of apoptosis induced by either oxidized AA or
oxidized EPA. On the basis of these results, it was concluded that both oxidized
n-3 or n-6 PUFAs induced apoptosis in HL-60 cells by a similar mechanism in a
CsA-insensitive manner and also that oxidized products of PUFAs, but not the
cellular oxidation process itself, play an important role in the mechanism of
apoptosis in HL-60 cells.
PMID: 12853075 [PubMed]
184: Menopause. 2003 Jul-Aug;10(4):322-31.
Isoflavone-rich soy protein prevents loss of hip lean mass but does not prevent
the shift in regional fat distribution in perimenopausal women.
Moeller LE, Peterson CT, Hanson KB, Dent SB, Lewis DS, King DS, Alekel DL.
Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City,
Iowa, USA.
OBJECTIVE: Menopause-induced estrogen deficiency increases the risk of
cardiovascular disease, which is related to a shift in regional fat
distribution. We tested the hypothesis that estrogen-like isoflavones in soy
protein isolate (SPI+) would lessen both regional fat gain and lean loss
compared with isoflavone-poor soy (SPI-). DESIGN: Perimenopausal participants (N
= 69) were randomly assigned (double-blind) to 24 weeks of treatment (40 g soy
or whey protein per day): SPI+ (n = 24), SPI- (n = 24), or whey control (n =
21); each participant had blood drawn in the fasted (12 hours) state, had
physical activity assessed, and kept a 5-day food diary. Dual-energy x-ray
absorptiometry was used to examine the effects of SPI+ on regional fat and lean
tissue distribution changes in the waist, hip, and thigh regions. RESULTS: Mean
body mass increased (P < 0.01) in each group, but treatment had no effect on
gain in overall body mass, fat mass, or lean mass using analysis of variance. In
all treatment groups combined, lean mass increased in each region; fat mass
increased only in the waist region. Treatment had an effect (P = 0.039) on hip
lean mass and a marginal effect (P = 0.077) on thigh fat. Regression analyses
revealed that SPI+ diminished the increase in thigh fat (P = 0.018) and
heightened the increase in hip lean (P = 0.035) mass. Carbohydrate intake (P =
0.006) and cohort (reflective of season; P = 0.011) contributed to the gain in
thigh fat. Total protein intake (P = 0.0012), plasma insulin (P = 0.0034), and
physical activity (P = 0.047) contributed to the gain in hip lean mass.
CONCLUSIONS: Gain in hip lean mass was greater (P = 0.014) in SPI+ than other
groups, but SPI+ did not reduce the disease-promoting menopausal shift in
regional fat mass.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12851515 [PubMed]
185: Lipids. 2003 Apr;38(4):431-5.
Docosapentaenoic acid does not completely replace DHA in n-3 FA-deficient rats
during early development.
Greiner RS, Catalan JN, Moriguchi T, Salem N Jr.
Laboratory of Membrane Biochemistry and Biophysics, National Institute on
Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland
20852, USA.
The reciprocal replacement of DHA by docosapentaenoic acid (DPAn-6) was studied
in rats that consumed an n-3 FA-deficient or n-3 FA-adequate diet. Dams were fed
the two experimental diets from weaning and throughout pregnancy and lactation.
Their pups were then fed the respective diets after weaning. Cortex FA analysis
was performed at various times (0, 5, 10, 20, 50, and 91 d) after birth to
determine whether DPAn-6 completely replaced DHA in the n-3-deficient group.
Cortical DHA levels were significantly lower (average 86%) in the n-3-deficient
rats. DPAn-6 increased significantly in the n-3-deficient rats starting with a
6.5-fold increase at day 0 up to a 54-fold increase at day 91 compared with the
n-3-adequate group. However, this significant increase did not completely
replace the loss of DHA at postnatal days 5, 10, and 20 in which there was still
an 11.5, 10.3, and 8.0% deficit in the sum of DHA and DPAn-6, respectively, in
the n-3-deficient group. Once docosatetraenoic (DTA) and arachidonic acids (AA)
were included in the sum (DHA + DPAn-6 + DTA + AA), the levels between the two
groups were similar. These results suggest that not only DPAn-6 but also other
n-6 FA, including DTA and AA, replace DHA in n-3-deficient rats. The lack of
total 22-carbon (22C) FA in the brain during the rapid membrane biogenesis that
occurs during early development could be a factor in the nervous system
functional deficits associated with n-3 FA deficiency.
PMID: 12848290 [PubMed]
186: Br J Nutr. 2003 Jul;90(1):207-14.
The effects of enterostatin intake on food intake and energy expenditure.
Kovacs EM, Lejeune MP, Westerterp-Plantenga MS.
Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
eva.kovacs@unilever.com
Enterostatin (ENT) has been found to inhibit food intake and selectively inhibit
fat intake in rats. Both peripheral and central mechanisms have been proposed.
It also has been suggested that ENT may increase thermogenesis. The present
study investigated the effects of oral ENT administration on food intake, energy
expenditure and body weight in subjects with a preference for a high-fat diet.
In a double-blind, placebo-controlled, randomized and crossover design, nine
female and three male healthy subjects (age 34 (sd 11) years, BMI 24.5 (sd 2.5)
kg/m(2)) with a preference for a high-fat diet ingested ENT (3 x 15 mg/d) or
placebo (PLA) while consuming a high-fat diet ad libitum for 4 d. Eight subjects
ended each intervention with a 36 h stay in the respiration chamber, continuing
the diet and treatment. Body-weight loss was significant (ENT 0.8 (se 0.3) kg,
P<0.05; PLA 1.3 (se 0.3) kg, P<0.001), but not different between treatments.
There was no difference between treatments in total energy intake (ENT 37.1 (se
2.6), PLA 35.9 (se 3.2) MJ), macronutrient composition, hunger, satiety and
hedonic scores during the 4 d high-fat diet. Energy expenditure (24 h) (ENT 9.6
(se 0.4), PLA 9.5 (se 0.4) MJ), sleeping and resting metabolic rate,
diet-induced thermogenesis, activity-induced energy expenditure and 24 h RQ (ENT
0.77 (se 0.01), PLA 0.77 (se 0.01)) were similar for both treatments. We
conclude that oral ENT administration did not affect food intake, energy
expenditure or body weight in subjects with a preference for a high-fat diet
experiencing a negative energy and fat balance.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12844393 [PubMed]
187: J Clin Endocrinol Metab. 2003 Jul;88(7):3005-10.
Comment in:
J Clin Endocrinol Metab. 2003 Jul;88(7):3003-4.
Interleukin-6 stimulates lipolysis and fat oxidation in humans.
van Hall G, Steensberg A, Sacchetti M, Fischer C, Keller C, Schjerling P,
Hiscock N, Moller K, Saltin B, Febbraio MA, Pedersen BK.
Copenhagen Muscle Research Center, Rigshospitalet, University of Copenhagen,
DK-2100 Copenhagen, Denmark. gvhall@cmrc.dk
Although IL-6 is a key modulator of immune function, it also plays a role in
regulating substrate metabolism. To determine whether IL-6 affects lipid
metabolism, 18 healthy men were infused for 3 h with saline (Con; n = 6) or a
high dose (High-rhIL6; n = 6) or a low dose (Low-rhIL6; n = 6) of recombinant
human IL-6 (rhIL-6). The IL-6 concentration during Con, Low-rhIL6, and
High-rhIL6 was at a steady state after 30 min of infusion at approximately 4,
140, and 320 pg/ml, respectively. Either dose of rhIL-6 was associated with a
similar increase in fatty acid (FA) concentration and endogenous FA rate of
appearance (R(a)) from 90 min after the start of the infusion. The FA
concentration and FA R(a) continued to increase until the cessation of rhIL-6
infusion, reaching levels approximately 50% greater than Con values. The
elevated levels reached at the end of rhIL-6 infusion persisted at least 3 h
postinfusion. Triacylglycerol concentrations were unchanged during rhIL-6
infusion, whereas whole body fat oxidation increased after the second hour of
rhIL-6 infusion. Of note, during Low-rhIL6, the induced elevation in FA
concentration and FA R(a) occurred in the absence of any change in adrenaline,
insulin, or glucagon, and no adverse side effects were observed. In conclusion,
the data identify IL-6 as a potent modulator of fat metabolism in humans,
increasing fat oxidation and FA reesterification without causing
hypertriacylglyceridemia.
Publication Types:
Clinical Trial
PMID: 12843134 [PubMed]
188: J Clin Invest. 2003 Jul;112(1):91-100.
The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty
liver diseases in mice.
Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ.
School of Biological Sciences, University of Auckland, Auckland, New Zealand.
a.xu@auckland.ac.nz
Adiponectin has recently been shown to be a promising candidate for the
treatment of obesity-associated metabolic syndromes. Replenishment of
recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin
resistance, and cause sustained weight loss without affecting food intake. Here
we report its potential roles in alcoholic and nonalcoholic fatty liver diseases
in mice. Circulating concentrations of adiponectin decreased significantly
following chronic consumption of high-fat ethanol-containing food. Delivery of
recombinant adiponectin into these mice dramatically alleviated hepatomegaly and
steatosis (fatty liver) and also significantly attenuated inflammation and the
elevated levels of serum alanine aminotransferase. These therapeutic effects
resulted partly from the ability of adiponectin to increase carnitine
palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while
it decreased the activities of two key enzymes involved in fatty acid synthesis,
including acetyl-CoA carboxylase and fatty acid synthase. Furthermore,
adiponectin treatment could suppress the hepatic production of TNF-alpha and
plasma concentrations of this proinflammatory cytokine. Adiponectin was also
effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase
abnormality associated with nonalcoholic obese, ob/ob mice. These results
demonstrate a novel mechanism of adiponectin action and suggest a potential
clinical application of adiponectin and its agonists in the treatment of liver
diseases.
PMID: 12840063 [PubMed]
189: Biol Trace Elem Res. 2003 Summer;93(1-3):127-40.
Effects of protein deficiency on liver trace elements and antioxidant activity
in carbon tetrachloride-induced liver cirrhosis.
Gonzalez-Reimers E, Lopez-Lirola A, Olivera RM, Santolaria-Fernandez F,
Galindo-Martin L, Abreu-Gonzalez P, Sanchez-Sanchez JJ, Martinez-Riera A.
Departamento de Medicina Interna, Hospital Universitario, Tenerife, Canary
Islands.
In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis,
ultimately leading to architectural distortion, liver circulatory changes, and
liver failure. Some data support the hypothesis that protein undernutrition may
play a role in the development and progression of nonalcoholic liver cirrhosis
and that this progression is at least partially mediated by changes in
glutathione peroxidase (GPX), superoxide dismutase (SOD), and other
antioxidative systems, leading to an increase in lipid peroxidation. We analyzed
the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon
tetrachloride (CCl4)-induced liver cirrhosis, the relation of protein
undernutrition and these trace elements with the activity of some hepatic
antioxidative enzymatic mechanisms, and the relation of all of them with
morphological and biochemical changes in 40 male adult Sprague-Dawley rats
divided in four groups. Liver cirrhosis was induced by intraperitoneal injection
of CCl4 to 10 rats fed a 2% protein diet and another 10 fed a 18% protein
control diet; two further groups included rats without cirrhosis fed the 2%
protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and
lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in
liver samples. We found that liver GPX and Se were reduced in the cirrhotic
animals, especially in the low-protein-fed ones, protein deficiency, but not
cirrhosis, exerting the main effects. A close correlation was found between
liver GPX and serum albumin and weight loss and an inverse one among GPX and
hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically
determined. These results suggest a pathogenetic role of decreased GPX in the
progression of liver disease, which may become enhanced by concomitant protein
undernutrition. In addition to iron, the levels of which were increased in the
malnourished rats, no differences were found regarding the other trace elements,
SOD activity, and lipid peroxidation products.
PMID: 12835497 [PubMed]
190: Int J Obes Relat Metab Disord. 2003 Jun;27(6):677-83.
Changes in abdominal subcutaneous fat water content with rapid weight loss and
long-term weight maintenance in abdominally obese men and women.
Laaksonen DE, Nuutinen J, Lahtinen T, Rissanen A, Niskanen LK.
1Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
OBJECTIVE: Insulin resistance decreases blood flow and volume in fat tissue. We
hypothesised that fat tissue nutritive blood flow and volume, and thereby water
content, would increase during weight loss and weight maintenance in obese
persons. DESIGN: Longitudinal clinical intervention with a 9-week
very-low-calorie diet (VLCD) followed by one year of weight maintenance.
SUBJECTS: Obese men (n=13) and women (n=14) with the metabolic syndrome.
MEASUREMENTS: Water content of abdominal subcutaneous fat tissue as estimated by
a sensor on the skin surface measuring the dielectric constant at 300 MHz.
Anthropometric measures of fatness and fat distribution. Biochemical measures
related to insulin resistance. RESULTS: Subjects lost 14.5+/-3.4% of body weight
during the VLCD, and generally sustained this weight loss during weight
maintenance. Insulin sensitivity as estimated by an index (qualitative insulin
sensitivity check index) increased during the VLCD, and remained increased
throughout weight maintenance. The dielectric constant increased from 23.3+/-2.3
to 25.0+/-2.1 (P<0.001) during the VLCD, and further to 27.8+/-1.9 (P<0.001)
during weight maintenance, indicating an increase in the water content of
subcutaneous fat. The increase in subcutaneous fat water content did not
correlate with weight loss and other measures of adiposity during the VLCD, but
there was an inverse correlation that strengthened in significance from baseline
to 6, 9 and 12 mo (r=-0.32 to -0.64, P=0.079-0.002). Increases in subcutaneous
fat water content also correlated with improvements in insulin sensitivity at 6,
9 and 12 months of weight maintenance (r=0.34-0.54, P=0.094-0.006). CONCLUSIONS:
Water content of abdominal subcutaneous adipose tissue increases with weight
loss in obese persons with the metabolic syndrome, and may reflect increased
subcutaneous fat tissue nutritive blood flow. The increase in water content
correlates with the increase in insulin sensitivity, suggesting that weight loss
and consequent improved insulin sensitivity could mediate the increase in
abdominal subcutaneous fat hydration.
Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial
PMID: 12833111 [PubMed]
191: Int J Obes Relat Metab Disord. 2003 Jun;27(6):648-56.
Exchanging carbohydrates for monounsaturated fats in energy-restricted diets:
effects on metabolic profile and other cardiovascular risk factors.
Colette C, Percheron C, Pares-Herbute N, Michel F, Pham TC, Brillant L, Descomps
B, Monnier L.
Laboratory of Human Nutrition and Atherogenesis, University Institute of
Clinical Research, Montpellier, Cedex, France.
colette@iurc1.iurc.montp.inserm.fr
OBJECTIVE: To investigate whether improvements in cardiovascular risk factors,
as observed in energy-balance conditions after exchanging carbohydrates (CHO)
for monounsaturated (MUFA) fats, are also observed in energy-restricted
conditions. DESIGN: Longitudinal, clinical intervention study using two types of
energy-restricted diets (-30% of initial energy intake) with similar levels of
saturated and polyunsaturated fats: a high CHO diet (55% of energy from CHOs,
10% from MUFAs) and a high MUFA diet (40% of energy from CHOs, 25% from MUFAs).
SUBJECTS: A total of 32 overweight subjects (nine males, 23 females, BMI: 26-45
kg/m(2)). MEASUREMENTS: Body weight, serum lipids, fasting plasma insulin and
phospholipid fatty acid composition of red blood cells were measured at baseline
and after 8 weeks. Various oxidative status parameters (plasma lipid
hydroperoxides, total plasma antioxidant capacity, plasma uric acid and vitamin
E) and serum-induced smooth muscular cell (SMC) proliferation were also measured
at these time points. RESULTS: Weight loss (1.1 kg/week over the first 4 weeks
and 6.7 kg at week 8) was not significantly affected by the diet composition.
Both diets reduced significantly total serum cholesterol, but the MUFA-rich diet
showed better effects on fasting serum triacylglycerol (TG) than the CHO-rich
diet: 1.18 vs 1.51 mmol/l for the MUFA-rich diet (after vs before, P<0.05) and
1.42 vs 1.62 for the CHO-rich diet. After 8 weeks, plasma vitamin E
concentrations were positively associated with the oleic acid level of red blood
cell phospholipids and showed opposite variations in both diets (increase with
the MUFA-rich diet and decrease with the CHO-rich diet). Relative changes in SMC
proliferation induced by sera were negatively associated with the ratio
oleic:linoleic acid of red blood cell phospholipids and were significantly
higher with the CHO-rich diet. CONCLUSIONS: The MUFA-rich diet showed better
effects on serum TG than the CHO-rich diet, even with energy restriction and
weight loss. The results suggest also a protective effect of oleic acid on
oxidative stress and SMC proliferation, two other important cardiovascular risk
factors.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12833107 [PubMed]
192: Diabetes Care. 2003 Jul;26(7):2069-74.
Effects of metformin and rosiglitazone monotherapy on insulin-mediated hepatic
glucose uptake and their relation to visceral fat in type 2 diabetes.
Iozzo P, Hallsten K, Oikonen V, Virtanen KA, Parkkola R, Kemppainen J, Solin O,
Lonnqvist F, Ferrannini E, Knuuti J, Nuutila P.
Turku PET Centre, Department of Nuclear Medicine, University of Turku, Turku,
Finland. patricia.iozzo@ifc.cnr
OBJECTIVE: Impaired insulin-mediated hepatic glucose uptake (HGU) has been
implicated in the hyperglycemia of type 2 diabetes. We examined the effects of
metformin (2 g/day) and rosiglitazone (8 mg/day) monotherapy on HGU and its
relation to subcutaneous fat, visceral fat (VF), and whole-body insulin-mediated
glucose metabolism in type 2 diabetic patients. RESEARCH DESIGN AND METHODS:
Glucose uptake was measured before and after 26 weeks of treatment using
positron emission tomography with [(18)F]2-fluoro-2-deoxyglucose during
euglycemic hyperinsulinemia; fat depots were quantified by magnetic resonance
imaging. RESULTS: Fasting plasma glucose levels were significantly decreased
after either rosiglitazone (-0.9 +/- 0.5 mmol/l) or metformin treatment (-1.1
+/- 0.5 mmol/l) in comparison with placebo; only metformin was associated with
weight loss (P < 0.02 vs. placebo). When controlling for the latter, the
placebo-subtracted change in whole-body glucose uptake averaged -1 +/- 4
micromol x min(-1) x kg(-1) in metformin-treated patients (NS) and +9 +/- 3
micromol x min(-1) x kg(-1) in rosiglitazone-treated patients (P = 0.01). Both
rosiglitazone and metformin treatment were associated with an increase in HGU;
versus placebo, the change reached statistical significance when controlling for
sex (placebo-subtracted values = +0.008 +/- 0.004 micromol x min(-1) x kg(-1) x
pmol/l(-1), P < 0.03, for metformin; and +0.007 +/- 0.004, P < 0.07, for
rosiglitazone). After treatment with either drug, insulin-mediated VF glucose
uptake (VFGU) was higher than with placebo. In the whole dataset, changes in HGU
were negatively related to changes in HbA(1c) (r = 0.43, P = 0.01) and
positively associated with changes in VFGU (r = 0.48, P < 0.01). CONCLUSIONS: We
conclude that both metformin and rosiglitazone monotherapy increase HGU in type
2 diabetes; direct drug actions, better glycemic control, and enhanced VF
insulin sensitivity are likely determinants of this phenomenon.
PMID: 12832315 [PubMed]
193: FEBS Lett. 2003 Jul 10;546(2-3):335-9.
Association of liver steatosis with lipid oversecretion and hypotriglyceridaemia
in C57BL/6j mice fed trans-10,cis-12-linoleic acid.
Degrace P, Demizieux L, Gresti J, Chardigny JM, Sebedio JL, Clouet P.
UPRES Lipides et Nutrition EA2422, Universite de Bourgogne, 6 bd Gabriel, 21000
Dijon, France.
Conjugated linoleic acids (CLA) have recently been recognized to reduce body fat
and plasma lipids in some animals. This study demonstrated that the steatosis
accompanying the fat loss induced by trans-10,cis-12-C(18:2) (CLA2) and not
cis-9,trans-11-C(18:2) (CLA1) isomer in C57BL/6j mice was not due to an
alteration of the liver lipoprotein production that was even increased. The
3-fold decrease in plasma triacylglycerol contents and the induction of mRNA
expression of low-density lipoprotein receptors concomitantly observed in
CLA2-fed mice suggested an increase in the lipoprotein clearance at the level of
the liver itself. CLA1 feeding produced similar but attenuated effects on
triglyceridaemia only.
PMID: 12832064 [PubMed]
194: Curr Sports Med Rep. 2002 Aug;1(4):208-13.
Weight loss and gain in athletes.
Rankin JW.
Department of Human Nutrition, Foods, and Exercise, Virginia Tech University,
Blacksburg, VA 24061-0430, USA. jrankin@vt.edu
Guidance from health professionals will assist the significant proportion of
athletes who desire a change in their body weight. Athletes who use drastic food
or fluid restriction to lose weight may experience negative consequences,
including loss of lean tissue, hormonal disturbances, and performance
impairment. Excess food consumption for weight gain can increase body fat and
risk factors for chronic diseases. Weight change is best done during the
off-season, modifying energy intake up or down by 500 kcal/d. Adequate
carbohydrate (60%-65%, > 5 g/kg) and protein (15%, 1.2-1.8 g/kg) and a low fat
intake (20%-25%) is appropriate for either weight loss or gain. The athletic
staff should be knowledgeable about the latest rules related to weight and
appropriate weight control methods so they may guide their athletes using
modest, safe approaches that will not negatively affect health or performance.
Publication Types:
Review
Review, Tutorial
PMID: 12831697 [PubMed]
195: Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E775-82. Epub 2003 Jun 24.
Effect of beta1- and beta2-adrenergic stimulation on energy expenditure,
substrate oxidation, and UCP3 expression in humans.
Hoeks J, van Baak MA, Hesselink MK, Hul GB, Vidal H, Saris WH, Schrauwen P.
NUTRIM, Department of Human Biology, Maastricht University, PO Box 616, 6200 MD
Maastricht, The Netherlands. j.hoeks@hb.unimaas.nl
In humans, beta-adrenergic stimulation increases energy and fat metabolism. In
the case of beta1-adrenergic stimulation, it is fueled by an increased
lipolysis. We examined the effect of beta2-adrenergic stimulation, with and
without a blocker of lipolysis, on thermogenesis and substrate oxidation.
Furthermore, the effect of beta1-and beta2-adrenergic stimulation on uncoupling
protein 3 (UCP3) mRNA expression was studied. Nine lean males received a 3-h
infusion of dobutamine (DOB, beta1) or salbutamol (SAL, beta2). Also, we
combined SAL with acipimox to block lipolysis (SAL+ACI). Energy and substrate
metabolism were measured continuously, blood was sampled every 30 min, and
muscle biopsies were taken before and after infusion. Energy expenditure
significantly increased approximately 13% in all conditions. Fat oxidation
increased 47 +/- 7% in the DOB group and 19 +/- 7% in the SAL group but remained
unchanged in the SAL+ACI condition. Glucose oxidation decreased 40 +/- 9% upon
DOB, remained unchanged during SAL, and increased 27 +/- 11% upon SAL+ACI.
Plasma free fatty acid (FFA) levels were increased by SAL (57 +/- 11%) and DOB
(47 +/- 16%), whereas SAL+ACI caused about fourfold lower FFA levels compared
with basal levels. No change in UCP3 was found after DOB or SAL, whereas SAL+ACI
downregulated skeletal muscle UCP3 mRNA levels 38 +/- 13%. In conclusion,
beta2-adrenergic stimulation directly increased energy expenditure independently
of plasma FFA levels. Furthermore, this is the first study to demonstrate a
downregulation of skeletal muscle UCP3 mRNA expression after the lowering of
plasma FFA concentrations in humans, despite an increase in energy expenditure
upon beta2-adrenergic stimulation.
Publication Types:
Clinical Trial
PMID: 12824081 [PubMed]