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Sexual dimorphism in adiposity is well described in adults, but the age at which differences first manifest is uncertain. Using a prospective cohort, we describe longitudinal changes in directly measured adiposity and intrahepatocellular lipid (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63 days, infants underwent quantification of adipose tissue depots by whole-body magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys and 30 girls). In the neonatal period girls are more adipose in relation to body size than boys. At follow-up (median age 63 days), girls remained significantly more adipose. The greater relative adiposity that characterises girls is explained by more subcutaneous adipose tissue and this becomes increasingly apparent by follow-up. No significant sex differences were seen in IHCL. Sex-specific differences in infant adipose tissue distribution are in keeping with those described in later life, and suggest that sexual dimorphism in adiposity is established in early infancy. [ABSTRACT FROM AUTHOR]

Background:Activation of the ileal brake, by infusing lipid directly into the distal part of the small intestine, alters gastrointestinal (GI) motility and inhibits food intake. The ileal brake effect on eating behavior of the other macronutrients is currently unknown.Objective:The objective of this study was to investigate the effects of ileal infusion of sucrose and casein on food intake, release of GI peptides, gastric emptying rate and small-bowel transit time with safflower oil as positive control.Design:This randomized, single-blind, crossover study was performed in 13 healthy subjects (6 male; mean age 26.4±2.9 years; mean body mass index 22.8±0.4 kg m−2) who were intubated with a naso-ileal catheter. Thirty minutes after the intake of a standardized breakfast, participants received an ileal infusion, containing control ((C) saline), safflower oil ((HL) 51.7 kcal), low-dose casein ((LP) 17.2 kcal) or high-dose casein ((HP) 51.7 kcal), low-dose sucrose ((LC) 17.2 kcal) and high-dose sucrose ((HC) 51.7 kcal), over a period of 90 min. Food intake was determined during an ad libitum meal. Visual analogue score questionnaires for hunger and satiety and blood samples were collected at regular intervals.Results:Ileal infusion of lipid, protein and carbohydrate resulted in a significant reduction in food intake compared with control (HL: 464.3±90.7 kcal, P<0.001; HP: 458.0±78.6 kcal, P<0.005; HC: 399.0±57.0 kcal, P<0.0001 vs control: 586.7±70.2 kcal, P<0.001, respectively). A reduction in energy intake was still apparent when the caloric amount of infused nutrients was added to the amount eaten during the ad libitum meal.Secretion of cholecystokinin and peptide YY but not of glucagon-like peptide-1 (7-36) was increased during ileal perfusion of fat, carbohydrates and protein. During ileal perfusion of all macronutrients, a delay in gastric emptying and intestinal transit was observed, but differences were not significant compared with control.Conclusion:Apart from lipids, also sucrose and casein reduce food intake on ileal infusion, thereby activating the ileal brake. In addition to food intake, also satiety and GI peptide secretion were affected. [ABSTRACT FROM AUTHOR]

Background:Irisin is a recently identified exercise-induced myokine suggested to induce browning of white adipocytes. Deficiency of myostatin, and thus stimulation of muscle growth, has also been reported to induce irisin and its precursor FNDC5 expression in muscle and drive the browning of white adipocytes in mice, implying that irisin may be related to muscle growth in addition to its beneficial effects in adipocytes. In humans, the effect of irisin in muscle hypertrophy as well as adipocyte metabolism has not been fully investigated.Methods:Primary cultured human myocytes/adipocytes and 3T3-L1 cells were used to examine irisin-regulated gene/protein expression. Lipid accumulation, ATP content, glycolysis, lipolysis and metabolite profile were measured in control and irisin-treated (10 and 50 nM) adipocytes.Results:In human myocytes, FNDC5 mRNA and irisin secretion were increased during myogenic differentiation, along with PGC1α and myogenin expression. Irisin treatment significantly increased insulin-like growth factor 1 and decreased myostatin gene expression through ERK pathway. PGC1α4, a newly discovered PGC1α isoform specifically related to muscle hypertrophy, was also upregulated. In human adipocytes, irisin induced uncoupling protein 1 and consequently increased adipocyte energy expenditure, expression of metabolic enzymes and metabolite intermediates, resulting in inhibition of lipid accumulation. Irisin and FNDC5 treatment also reduced preadipocyte differentiation, suggesting an additional mechanism in suppressing fat mass.Conclusions:These results suggest that irisin/FNDC5 has a pleiotropic role in muscle and improvement of adipocyte metabolism in humans. [ABSTRACT FROM AUTHOR]

Objective:To investigate the effects of weight loss due to laparoscopic sleeve gastrectomy (LSG) on erythrocyte aggregation and the relationship of anthropometric and plasmatic factors, such as plasma viscosity, fibrinogen and lipids, with erythrocyte aggregation.Design and subjects:The RBC aggregation and kinetics of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser (LORCA). Before the LSG and 6 and 12 months after the LSG, we evaluated the aggregation index (AI), amplitude (AMP) and aggregation half-time (t1/2), plasma viscosity, fibrinogen, glucose and lipids patterns in 15 non-diabetic obese subjects.Results:The static and kinetic parameters of aggregation in obese patients at each time point after bariatric weight loss surgery were calculated and significant differences were observed at 12 months after surgery. AI and AMP decreased from 69.81±5.12% and 27.43±2.9 a.u. at baseline to 64.91±5.94% and 22.15±4.3 a.u. 12 months after surgery, respectively. The t1/2 increased from 1.7 (1.32-2.24) s at baseline compared with 2.02 (1.68-2.42) s at 12 months after the surgery. Plasma viscosity and fibrinogen decreased from 1.50±0.093 mPa s and 3.0±0.41 g l−1 at baseline to 1.407±0.062 mPa s and to 2.66±0.25 g l−1 12 months after surgery, respectively. AI correlated positively with BMI (r=0.74, P=0.001), waist circumference (r=0.68, P=0.005), fibrinogen (r=0.52, P=0.045) and plasma viscosity (r=0.76, P=0.001) and negatively with percentages of weight lost after surgery (r=−0.54, P=0.034). Multivariate analyses found that the BMI, fibrinogen and plasma viscosity independently influenced the AI.Conclusion:The study demonstrated that weight loss due to restrictive bariatric surgery can beneficially affect red cell aggregation parameters. The improvement of the RBC aggregation behaviours among obese subjects with weight loss due to LSG was associated with changes in plasmatic factors, especially fibrinogen. [ABSTRACT FROM AUTHOR]

Background/Objectives:Glycerol represents an important metabolite for the control of lipid accumulation and hepatic gluconeogenesis. We investigated whether hepatic expression and functionality of aquaporin-9 (AQP9), a channel mediating glycerol influx into hepatocytes, is impaired in non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in the context of insulin resistance.Subjects/Methods:Liver biopsies were obtained from 66 morbid obese patients undergoing bariatric surgery (66% women, mean body mass index (BMI) 46.1±1.0 kg m−2) with available liver echography and pathology analysis of the biopsies in this cross-sectional study. Subjects were classified according to normoglycemia (NG), impaired glucose tolerance (IGT) or type 2 diabetes (T2D). Hepatic expression of AQP9 was analyzed by real-time PCR, western blotting and immunohistochemistry, while glycerol permeability (Pgly) was measured by stopped-flow light scattering.Results:AQP9 was the most abundantly (P<0.0001) expressed aquaglyceroporin in human liver (AQP9>>>AQP3>AQP7>AQP10). Obese patients with T2D showed increased plasma glycerol as well as lower Pgly and hepatic AQP9 expression. The prevalence of NAFLD and NASH in T2D patients was 100 and 65%, respectively. Interestingly, AQP9 expression was decreased in patients with NAFLD and NASH as compared with those without hepatosteatosis, in direct relation to the degree of steatosis and lobular inflammation, being further reduced in insulin-resistant individuals. The association of AQP9 with insulin sensitivity was independent of BMI and age. Consistent with these data, fasting insulin and C-reactive protein contributed independently to 33.1% of the hepatic AQP9 mRNA expression variance after controlling for the effects of age and BMI.Conclusions:AQP9 downregulation together with the subsequent reduction in hepatic glycerol permeability in insulin-resistant states emerges as a compensatory mechanism whereby the liver counteracts further triacylglycerol accumulation within its parenchyma as well as reduces hepatic gluconeogenesis in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Background:3T3-L1 cells have been widely used as a model for adipogenesis. However, despite its popularity, differentiation of this cell line has been reported to be inconsistent with low efficiency.Objective:To investigate the effect of media height during adipocyte differentiation on lipid accumulation and adipokine secretion in mature adipocytes.Methods:Three cell lines (3T3-L1, OP9 and ChubS7) were used to test the influence of media volume on adipogenesis. Total lipid content and lipid droplet size and number were quantified. Adipocyte related gene expressions were quantified during the course of differentiation. Secretion of leptin and adiponectin from mature adipocytes were measured using enzyme-linked immunosorbent assays. The influence of oxygen partial pressure on adipogenesis was investigated using three oxygen percentages: 5, 21 and 30%. Insulin sensitivity was measured by insulin inhibition of isoproterenol-induced lipolysis and phosphorylation of insulin receptor substrate-1.Results:A lower media height during adipogenesis increased total lipid accumulation, NEFA release and leptin and adiponectin secretion in mature adipocytes. Insulin sensitivity was not affected by media height during differentiation.Conclusion:Media height during adipogenesis was inversely correlated with lipid content in mature adipocytes. To achieve a high lipid content and greater adipokine secretion, it is best to use a low media volume during differentiation. [ABSTRACT FROM AUTHOR]

Objective:Obesity is associated with an increase in various pro-inflammatory and anti-inflammatory cytokines, but the interplay of these cytokines is incompletely understood. We conducted experiments to test a broader hypothesis that a dynamic interplay of pro-inflammatory and anti-inflammatory cytokines controls lipid storage in adipocytes.Design:Three experiments were designed to test the overall hypothesis that proinflammatory cytokine (for example, tumor necrosis factor-α (TNF-α) inhibits anti-inflammatory cytokine (for example, adiponectin) activity in an attempt to limit excess lipid accumulation in adipocytes.Results:Experiment one showed that in pro-inflammatory animal models (ap2-P65, ob/ob and high-fat diet-induced obese mice), the increase in TNF-α expression was associated with a decrease in adiponectin expression. Experiment two showed that in 3T3-L1 adipocytes, TNF-α significantly reduced lipid accumulation and glucose uptake induced by adiponectin, and increased lipolysis. Experiment three showed that in 3T3-L1 adipocytes, TNF-α reduced mRNA and protein expression of adiponectin. Adiponectin gene transcription and mRNA stability were both reduced by TNF-α. The expression of peroxisome proliferator-activated receptor gamma, an activator of adiponectin gene promoter, was reduced by TNF-α. The inhibitory activity of TNF-α was blocked by the chemical inhibitors of NF-κB and super suppressor IκBα.Conclusions:TNF-α opposes the action of adiponectin in the regulation of lipid metabolism, and inhibits adiponectin expression at transcriptional and post-transcriptional levels. The results suggest that pro-inflammatory cytokine inhibit anti-inflammatory cytokine in adipocytes to reduce lipid storage. This suggests a potential role of anti-inflammatory cytokines in the control of adipose tissue expansion. [ABSTRACT FROM AUTHOR]

Objective:The skeletal muscle of obese humans is characterized by an inability to appropriately respond to alterations in substrate availability. The purpose of this study was to determine if this metabolic inflexibility with obesity is retained in mitochondria of human skeletal muscle cells raised in culture (HSkMC) and to identify potential mechanisms involved.Design:Mitochondrial respiration was measured in permeabilized myotubes cultured from lean and obese individuals before and after a 24-h lipid incubation.Results:Mitochondrial respiration (state 3) in the presence of lipid substrate (palmitoyl carnitine) increased by almost twofold after lipid incubation in HSkMC from lean, but not obese subjects, indicative of metabolic inflexibility with obesity. The 24-h lipid incubation increased mitochondrial DNA (mtDNA) copy number in HSkMC from lean subjects by +16% (P<0.05); conversely, mtDNA copy number decreased in myotubes cultured from obese individuals (−13%, P=0.06). When respiration data were normalized to mtDNA copy number and other indices of mitochondrial content (COX-IV protein content and CS activity), the significant treatment effects of lipid incubation persisted in the lean subjects, suggesting concomitant alterations in mitochondrial function; no similar adjustment was evident in HSkMC from obese individuals.Conclusion:These data indicate that the skeletal muscle of obese individuals inherently lacks metabolic flexibility in response to lipid exposure, which consists of an inability to increase mitochondrial respiration in the presence of lipid substrate and perhaps by an inability to induce mitochondrial proliferation. [ABSTRACT FROM AUTHOR]

Objective:Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years.Design:A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers.Subjects:A total of 564 adults (n=90-98 per group; body mass index 30-40 kg m−2) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90-95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007-April 2009 and is registered with Clinicaltrials.gov, number NCT00480909.Results:From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7-8.0) more weight than those on placebo and 3.8 kg (1.6-6.0) more than those on orlistat (P0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids.Conclusion:Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Objective:To examine in mice the acute effects of epigallocatechin gallate (EGCG), a green tea bioactive polyphenol on substrate metabolism with focus on the fate of dietary lipids.Methods:Male C57BL/6 mice were fed high-fat diets supplemented with EGCG extracted from green tea (TEAVIGO, DSM Nutritional Products Ltd, Basel, Switzerland) at different dosages up to 1% (w/w). Effects of EGCG on body composition (quantitative magnetic resonance), food intake and digestibility, oxidation and incorporation of exogenous lipids (stable isotope techniques: 13C-labeled palmitate and diet supplemented with corn oil as a natural source of 13C-enriched lipids) as well as gene expression (quantitative real-time PCR) in liver and intestinal mucosa were investigated.Results:Short-term supplementation (4-7 days) of dietary EGCG increased energy excretion, while food and energy intake were not affected. Fecal energy loss was accompanied by increased fat and nitrogen excretion. EGCG decreased post-prandial triglyceride and glycogen content in liver, increased oxidation of dietary lipids and decreased incorporation of dietary 13C-enriched lipids into fat tissues, liver and skeletal muscle. EGCG dose dependently reversed high-fat diet-induced effects on intestinal substrate transporters (CD36, FATP4 and SGLT1) and downregulated lipogenesis-related genes (ACC, FAS and SCD1) in liver in the post-prandial state.Conclusions:Anti-obesity effects of EGCG can be explained by a decreased food digestibility affecting substrate metabolism of intestinal mucosa and liver, leading to increased post-prandial fat oxidation and reduced incorporation of dietary lipids into tissues. [ABSTRACT FROM AUTHOR]

Background:Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS.Objective:This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS.Design:A free-living, single-blinded dietary intervention study.Subjects and Methods:MetS subjects (n=417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined.Results:In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P<0.01), particularly in men.Conclusion:There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles. [ABSTRACT FROM AUTHOR]

Objective:To investigate the impact of reduced adipocyte fatty acid-binding protein 4 (FABP4) in control of body weight, glucose and lipid homeostasis in diet-induced obese (DIO) mice.Methods:We applied RNA interference (RNAi) technology to generate FABP4 germline knockdown mice to investigate their metabolic phenotype.Results:RNAi-mediated knockdown reduced FABP4 mRNA expression and protein levels by almost 90% in adipocytes of standard chow-fed mice. In adipocytes of DIO mice, RNAi reduced FABP4 expression and protein levels by 70 and 80%, respectively. There was no increase in adipocyte FABP5 expression in FABP4 knockdown mice. The knockdown of FABP4 significantly increased body weight and fat mass in DIO mice. However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity.Conclusion:Our data indicate that robust knockdown of FABP4 increases body weight and fat mass without improving glucose and lipid homeostasis in DIO mice. [ABSTRACT FROM AUTHOR]

Objective:Mice from a long-term selective breeding experiment for high voluntary wheel running offer a unique model to examine the contributions of genetic and environmental factors in determining the aspects of behavior and metabolism relevant to body-weight regulation and obesity. Starting with generation 16 and continuing through to generation 52, mice from the four replicate high runner (HR) lines have run 2.5–3-fold more revolutions per day as compared with four non-selected control (C) lines, but the nature of this apparent selection limit is not understood. We hypothesized that it might involve the availability of dietary lipids.Methods:Wheel running, food consumption (Teklad Rodent Diet (W) 8604, 14% kJ from fat; or Harlan Teklad TD.88137 Western Diet (WD), 42% kJ from fat) and body mass were measured over 1–2-week intervals in 100 males for 2 months starting 3 days after weaning.Results:WD was obesogenic for both HR and C, significantly increasing both body mass and retroperitoneal fat pad mass, the latter even when controlling statistically for wheel-running distance and caloric intake. The HR mice had significantly less fat than C mice, explainable statistically by their greater running distance. On adjusting for body mass, HR mice showed higher caloric intake than C mice, also explainable by their higher running. Accounting for body mass and running, WD initially caused increased caloric intake in both HR and C, but this effect was reversed during the last four weeks of the study. Western diet had little or no effect on wheel running in C mice, but increased revolutions per day by as much as 75% in HR mice, mainly through increased time spent running.Conclusion:The remarkable stimulation of wheel running by WD in HR mice may involve fuel usage during prolonged endurance exercise and/or direct behavioral effects on motivation. Their unique behavioral responses to WD may render HR mice an important model for understanding the control of voluntary activity levels. [ABSTRACT FROM AUTHOR]

Objective:The immediate cause of obesity is the massive deposition of subcutaneous and visceral fat attributing to the continuous proliferation and differentiation of preadipocytes. The identification of the underlying molecular mechanisms of preadipocytes differentiation is urgent, and will have an important role in plastic and reconstructive surgical procedures.Methods:Two small hairpin RNA (shRNA)-mediated RNA interference plasmids have been constructed on the basis of the activity of H1 promoter-driven expression vector psiRNA-hH1neo to suppress the expression of angiotensinogen (AGT) in human preadipocytes-visceral (HPA-v). Subsequently, glycerol-3-phosphate dehydrogenase (G3PDH) activity and intracytoplasmic lipids content were detected during the process of HPA-v differentiation.Results:Small hairpin RNA-expressing vectors have been successfully constructed to suppress the expression of AGT significantly. Both intracytoplasmic lipids content and G3PDH activity decreased to a certain extent compared with that in the control group in the whole process of HPA-v differentiation.Conclusions:Two shRNA-mediated AGT-targeting plasmids inhibited the process of HPA-v differentiation to a certain extent. However, the accumulation of intracytoplasmic lipids was not exclusively determined by the expression of AGT, and it may also be regulated by other factors. In conclusion, this study provided a method to inhibit the process of preadipocytes differentiation, and it may have a role in obesity treatment and adipose tissue engineering application. [ABSTRACT FROM AUTHOR]

Background:LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells) is a member of the tumor necrosis factor (TNF) family, primarily expressed in lymphocytes, which was associated with the induction of pro-inflammatory cytokines and alterations of lipid homeostasis in animal models. We aimed to analyze whether LIGHT has a role in the human obesity-associated inflammatory status.Methods:The association between circulating LIGHT concentrations and clinical variables was studied in 190 subjects with different degrees of obesity and glucose tolerance. The expression and release of 21 different cytokines, and the expression of genes involved in lipid metabolism were also evaluated after stimulation with LIGHT in cultured human differentiated adipocytes.Results:Serum LIGHT concentrations positively associated with body mass index (BMI), fat mass, glycated hemoglobin and fasting triglycerides, and negatively with high-density lipoprotein cholesterol. Circulating LIGHT concentrations were significantly increased in morbidly obese subjects and in patients with type 2 diabetes. LIGHT induced the secretion of several cytokines and upregulated the expression and secretion of interleukin-6 (IL-6), IL-8, Growth Regulated Oncogene (GRO) and monocyte chemotactic protein-1 (MCP-1). These observations were concomitant with the activation of nuclear factor (NF)-κB signalling in human differentiated adipocytes. LIGHT also upregulated the expression and synthesis of its own receptor (herpesvirus entry mediator (HVEM)) and decreased the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and fatty acid synthase.Conclusion:These data suggest that LIGHT may have a role in mediating chronic inflammation and alterations of lipid metabolism in obese subjects. [ABSTRACT FROM AUTHOR]

Objective:Childhood obesity is a growing global epidemic. Recent studies indicate that obesity and related metabolic traits are highly heritable. Increasing evidence suggests that growth hormone (GH) and the insulin-like growth factor-I (IGF-I) axis have important functions in regulating adiposity and insulin sensitivity. Five single-nucleotide polymorphisms (SNPs) at IGF-binding protein-3 (IGFBP3) were genotyped to find their associations with IGF-1 activity level and common clinical metabolic traits.Patients and Methods:We examined the associations of five SNPs at IGFBP3 with serum IGF-I and IGFBP-3 levels, as well as with obesity-related metabolic traits in 981 Hong Kong Chinese adolescents. Factor analysis was used to reduce the intercorrelated variables to five factor scores indicating body composition, blood pressure, IGF-I activity, triglyceride (TG)+high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC)+low-density lipoprotein cholesterol (LDL-C) factor scores.Results:There was a strong association between the −202A/C polymorphism (rs2854744) and IGF-I activity (P=1.2 × 10−6) and TC+LDL-C factor scores (P=0.0085), corrected for age and sex. The C allele was associated with decreased IGFBP-3 levels (P=1.21 × 10−13), increased IGF-I/IGFBP-3 molar ratio (P=5.22 × 10−6) and decreased LDL-C (P=0.020). There was also a significant association between a G/A polymorphism at the 3′ flanking sequence (rs13223993) of the IGFBP3 gene and the TG+HDL-C factor score (P=0.0013). The minor A allele carriers of rs13223993 had a lower HDL-C (P=0.0067) level and a tendency toward a high TG level. Haplotype analysis did not increase the significance of associations between single SNPs and phenotypes.Conclusion:Our results support the function of IGFBP3 gene polymorphisms in modulating IGF-I activity and lipid levels in adolescents. Given the prognostic significance of IGF-I, IGFBPs and lipids on risk of diabetes, obesity and cancer, long-term studies are required to clarify the clinical meaning of these findings. [ABSTRACT FROM AUTHOR]

Objective:To determine whether proanthocyanidins can protect against dyslipidemia induced by a high-fat diet (HFD) and to address the mechanisms that underlie this hypolipidemic effect.Design and measurements:Female Wistar rats were fed on a HFD for 13 weeks. They were divided into two groups, one of which was treated with a grape seed proanthocyanidin extract (25 mg kg−1 of body weight) for 10 days. Plasma and liver lipids were measured by colorimetric and gravimetric analysis. Liver, muscle and adipose tissue were used to study the expression of genes involved in the synthesis and oxidation of fatty acids and lipoprotein homeostasis by real-time RT-PCR.Results:The administration of proanthocyanidins normalized plasma triglyceride and LDL-cholesterol (both parameters significantly increased with the HFD) but tended to decrease hypercholesterolemia and fatty liver. Gene expression analyses revealed that proanthocyanidins repressed both the expression of hepatic key regulators of lipogenesis and very low density lipoprotein (VLDL) assembling such as SREBP1, MTP and DGAT2, all of which were overexpressed by the HFD.Conclusion:These findings indicate that natural proanthocyanidins improve dyslipidemia associated with HFDs, mainly by repressing lipogenesis and VLDL assembly in the liver, and support the idea that they are powerful agents for preventing and treating lipid altered metabolic states. [ABSTRACT FROM AUTHOR]

Objectives:The orexigenic hormone ghrelin circulates mainly in two forms, acylated and desacyl ghrelin. We evaluated the impact of obesity and obesity-associated type 2 diabetes (T2D) on ghrelin forms and the potential role of acylated and desacyl ghrelin in the control of adipogenesis in humans.Methods:Plasma concentrations of the different ghrelin forms were measured in 80 subjects. The expression of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) was analyzed in omental adipose tissue using western blot and immunohistochemistry, and the effect of acylated ghrelin and desacyl ghrelin (0.1–1000 pmol l−1) on adipogenesis was determined in vitro in omental adipocytes.Results:Circulating concentrations of acylated ghrelin were increased, whereas desacyl ghrelin levels were decreased, in obesity and obesity-associated T2D. Body mass index, waist circumference, insulin and HOMA (homeostasis model assessment) index were positively correlated with acylated ghrelin levels. Obese individuals showed a lower protein expression of GHS-R in omental adipose tissue. In differentiating omental adipocytes, incubation with both acylated and desacyl ghrelin significantly increased PPARγ (peroxisome proliferator-activated receptor γ) and SREBP1 (sterol-regulatory element binding protein-1) mRNA levels, as well as several fat storage-related proteins, including acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase and perilipin. Consequently, both the ghrelin forms stimulated intracytoplasmatic lipid accumulation.Conclusions:Both acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Given the lipogenic effect of acylated ghrelin on visceral adipocytes, the herein-reported elevation of its circulating concentrations in obese individuals may play a role in excessive fat accumulation in obesity.International Journal of Obesity (2009) 33, 541–552; doi:10.1038/ijo.2009.40; published online 24 February 2009 [ABSTRACT FROM AUTHOR]

Alcohol (ethanol) is consumed on a daily basis by a large fraction of the population, and in many countries, light-to-moderate alcohol consumption is considered as an integral part of the diet. Although the relationship between alcohol intake and obesity is controversial, regular consumption of alcohol, through its effects in suppressing fat oxidation, is regarded as a risk factor for weight gain, increased abdominal obesity and hypertriglyceridemia. Indeed, alcohol taken with a meal leads to an increase in postprandial lipemia—an effect on postprandial metabolism that is opposite to that observed with exercise. Furthermore, although regular exercise training and/or a preprandial exercise session reduce postprandial lipemia independently of alcohol ingestion, the exercise-induced reduction in postprandial lipemia is nonetheless less pronounced when alcohol is also consumed with the meal. Whether or not alcohol influences exercise and sport performance remains contradictory. It is believed that alcohol has deleterious effects on the performance, although it may contribute to reduce pain and anxiety. The alcohol effects on sports performance depend on the type and dosage of alcohol, acute vs chronic administration, the alcohol elimination rate as well as the type of exercise.International Journal of Obesity (2008) 32, S48–S52; doi:10.1038/ijo.2008.206 [ABSTRACT FROM AUTHOR]

Background:In adults, circulating aP2 may link obesity, inflammation and the metabolic syndrome, but there are few data in children. Experimental models support that dietary factors, particularly dietary fat, may be major determinants of phenotype.Objective:The aim of this study was to investigate, in normal, overweight and obese children, the relationships among aP2, the metabolic syndrome, inflammation and diet.Design:This was a cross-sectional study conducted in Northern Switzerland.Subjects:Subjects for this study were 6- to 14-year-old, prepubertal and early pubertal, normal weight, overweight and obese children (n=124).Main outcome measures:Body mass index (BMI), body fat percent, waist-to-hip ratio, blood pressure, circulating aP2, fasting insulin, C-reactive protein (CRP), plasma lipids and dietary intakes of macro- and micronutrients were determined.Results:Circulating aP2 markedly increased with increasing central and total adiposity, and predicted measures of insulin resistance. Independent of BMI standard deviation scores and puberty, aP2 correlated with intake of the antioxidant vitamins A, C and E as well as circulating concentrations of CRP, leptin and low-density lipoprotein cholesterol. Children with lower aP2 concentrations consuming high-fat diets did not show an increase in fasting insulin or CRP, whereas those with higher aP2 concentrations showed marked increases in these measures with high intakes of fat or saturated fat.Conclusions:Increased central and overall adiposity in children are associated with higher circulating aP2 concentrations. In children with high dietary intakes of total fat and saturated fat, but not those with low intakes, higher aP2 concentrations are associated with measures of insulin resistance and inflammation.International Journal of Obesity (2008) 32, 1513–1520; doi:10.1038/ijo.2008.128; published online 5 August 2008 [ABSTRACT FROM AUTHOR]

Objective:The severity of obesity is often more determined by the distribution of fat depots rather than by body weight itself. Therefore, the effect of rimonabant on fat distribution pattern was investigated in female candy-fed Wistar rats.Design:Female Wistar rats were fed a high fat, high carbohydrate (candy-) diet for 12 weeks. During the last 6 weeks rats were treated with rimonabant. Food intake and body weight development were investigated, as well as effects on total body fat, especially visceral fat and ectopic lipid accumulation in skeletal muscle and liver, determined by in vivo magnetic resonance imaging/magnetic resonance spectroscopy.Results:Candy-diet increased body weight, which was predominantly due to the increased total fat mass with predominance of visceral fat accumulation. Treatment with rimonabant fully reversed the weight gain and fat deposition in the visceral cavity and skeletal muscle, in contrast to pair feeding. In spite of an only transient reduction of food intake, body weight reduction, as well as normalized body fat, reduced visceral fat and intramyocellular lipids were maintained over the treatment period.Conclusions:We conclude that additional factors other than reduced caloric intake must be responsible for the improvements in these lipid parameters. The complete cluster of results is consistent with increased lipid oxidation caused by rimonabant.International Journal of Obesity (2008) 32, 1363–1372; doi:10.1038/ijo.2008.105; published online 15 July 2008 [ABSTRACT FROM AUTHOR]

Objective:To assess the effects of fish (lean or oily) and fish oil consumption on blood lipid concentration during weight loss.Design:Randomized, controlled 8-week trial of energy-restricted diet varying in fish and fish oil content. Subjects, 324 men and women, aged 20–40 years, body mass index 27.5–32.5 kg m−2, from Iceland, Spain and Ireland, were randomized to one of four groups: (1) control (sunflower oil capsules, no seafood), (2) cod diet (3 × 150 g week−1), (3) salmon diet (3 × 150 g week−1), (4) fish oil (DHA/EPA capsules, no seafood). The macronutrient composition of the diets was similar between the groups and the capsule groups were single-blinded.Measurements:Total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein cholesterol, triacylglycerol (TG) and anthropometrics were measured at baseline and end point.Results:The difference in logTG lowering between the control group and the cod diet, salmon diet and fish oil from baseline to end point was −0.036 (95% CI −0.079 to 0.006), −0.060 (−0.101 to −0.018) and −0.037 (−0.079 to 0.006), respectively. Reduction in TC was about 0.2 mmol l−1 greater in the fish groups (cod and salmon) than in the control group, but only of borderline significance when adjusting for weight loss. HDL tended to decrease less in the diet groups consuming a significant amount of n-3 fatty acids (salmon and fish oil).Conclusion:Weight-loss diet including oily fish resulted in greater TG reduction than did a diet without fish or fish oil. Controlled trials using whole fish as a test meal are encouraged to be able to elucidate the role of different constituents of fish for human health.International Journal of Obesity (2008) 32, 1105–1112; doi:10.1038/ijo.2008.64; published online 20 May 2008 [ABSTRACT FROM AUTHOR]

Background:High-intensity progressive resistance training (PRT) improves adiposity and metabolic risk in adults, but has not been investigated in children within a randomized controlled trial (RCT).Objective:We hypothesized that high-intensity PRT (8 weeks, twice a week) would decrease central adiposity in children, as assessed via waist circumference.Methods Design/Setting/Participants:Concealed randomization stratified by age and gender was used to allocate rural New Zealand school students to the wait-list control or PRT group.Intervention:Participants were prescribed two sets (eight repetitions per set) of 11 exercises targeting all the major muscle groups at high intensity.Primary Outcome:Waist circumference; secondary outcomes included whole body fat, muscular fitness (one repetition maximum), cardiorespiratory fitness (peak oxygen consumption during a treadmill test), lipids, insulin sensitivity and fasting glucose.Results:Of the 78 children (32 girls and 46 boys; mean age 12.2(1.3) years), 51% were either overweight (33%) or obese (18%). High-intensity PRT significantly improved waist circumference (mean change PRT −0.8 (2.2) cm vs +0.5 (1.7) cm control; F=7.59, P=0.008), fat mass (mean change PRT +0.2 (1.4) kg vs +1.0 (1.2) kg control; F=6.00, P=0.017), percent body fat (mean change PRT –0.3 (1.8)% vs +1.2 (2.1)% control; F=9.04, P=0.004), body mass index (mean change PRT −0.01 (0.8) kg m−2 vs +0.4 (0.7) kg m−2 control; F=6.02, P=0.017), upper body strength (mean change PRT+11.6(6.1) kg vs +2.9(3.7) kg control; F=48.6, P<0.001) and lower body strength (mean change PRT +42.9(26.6) kg vs +28.5(26.6) kg control; F=4.72, P=0.034) compared to the control group. Waist circumference decreased the most in those with the greatest baseline relative strength (r=−0.257, P=0.036), and greatest relative (r=−0.400, P=0.001) and absolute (r=0.340, P=0.006) strength gains during the intervention.Conclusion:Isolated high-intensity PRT significantly improves central and whole body adiposity in association with muscle strength in normal-weight and overweight children. The clinical relevance and sustainability of these changes in adiposity should be addressed in future long-term studies.International Journal of Obesity (2008) 32, 1016–1027; doi:10.1038/ijo.2008.5; published online 19 February 2008 [ABSTRACT FROM AUTHOR]

Objective:Much has been written on the metabolic syndrome and related recent criteria. However, it remains unclear whether such criteria help clinical practice. This review will evaluate the usefulness of metabolic syndrome criteria to enhance risk prediction for either cardiovascular disease or diabetes.Design:This is a narrative review that is based on the author's experience from relevant publications from his group and from other related research.Results:Although the presence of metabolic syndrome, however defined, is clearly associated with higher risk for vascular disease, the criteria do not enhance coronary heart disease (CHD) prediction from simpler Framingham-based risk scores. The dichotomous nature of metabolic syndrome criteria—either you have it or you do not—combined with the lack of age, low-density lipoprotein cholesterol and smoking account for their inferior predictive value. Metabolic syndrome criteria are, in fact, more strongly associated with incident diabetes, an observation demonstrated in the West of Scotland Coronary Prevention Study (WOSCOPS). This is because three of the five parameters within metabolic syndrome criteria (waist, glucose and triglyceride) are more closely linked to risk for diabetes than risk for CHD. However, screening for prevalent or high risk of incident diabetes is a complex and debated issue and is by no means guaranteed to be widely adopted.Conclusions:Metabolic syndrome criteria do not offer benefits beyond established methods of vascular risk assessment. Thus, the focus in clinical practice should remain on established risk factors (for example, smoking, lipids, blood pressure) both to determine CHD risk, through established charts, and to reduce it.International Journal of Obesity (2008) 32, S30–S34; doi:10.1038/ijo.2008.33 [ABSTRACT FROM AUTHOR]

Objective:To investigate the prevalence of metabolic syndrome and its associated risk factors in a cohort of university freshmen.Design:A cross-sectional study in a university health center in North Taiwan.Subjects:A total of 8226 students (mean age: 19.2±2.3 years) receiving pre-entrance health examinations and lifestyle questionnaires during the 2005–2006 academic year were recruited.Measurements:A fasting plasma glucose, lipids, uric acid and hepatitis B serology were measured for each subject. The prevalence of metabolic syndrome and its individual components were examined using the America Heart Association and National Heart Lung Blood Institute criteria. The risk factors for metabolic syndrome were identified using a multivariate logistic regression analysis.Results:The prevalence of overweight, obesity and metabolic syndrome was 12.7% (17.0% in men and 7.6% in women), 13.0% (18.4% in men and 6.4% in women) and 4.6% (6.4% in men and 2.4% in women). The risk for metabolic syndrome increased with an increase of body mass index and plasma uric acid level, and decreased with the vigorous physical activity and current alcohol drinking. Furthermore, as compared to subjects with seroprotective titers from hepatitis B vaccination (anti-HBs(+) and anti-HBc(−)), those without protective titers of anti-HBs after vaccination or without hepatitis B infection (anti-HBs(−) and anti-HBc(−)) had 34% higher risk for metabolic syndrome, and those with natural infection of hepatitis B (anti-HBc(+)) had 58% higher risk for metabolic syndrome.Conclusions:Overweight, obesity and metabolic syndrome were more common among men than women in university freshmen. Hepatitis B vaccination with anti-HBs(+) was associated with a lower risk of metabolic syndrome as compared to anti-HBs(−). However, hepatitis B infection presented with anti-HBc(+) was associated with a higher risk of metabolic syndrome. The interplay between hepatitis B infection, hepatitis B vaccination and metabolic syndrome needs further investigation.International Journal of Obesity (2008) 32, 474–480; doi:10.1038/sj.ijo.0803753; published online 23 October 2007 [ABSTRACT FROM AUTHOR]

Objective:Obese patients with schizophrenia being treated with clozapine and non-psychiatric obese are often assumed to share the same physiological changes in obesity. The aim of this study was to identify possible metabolic and hormonal differences between non-psychiatric obese subjects (OB) and obese patients with schizophrenia being treated with clozapine (OSC).Subjects:Fifty-one normal healthy subjects (Nor, body mass index (BMI):23.2±0.3), 50 OB (BMI:31.7±0.7) and 71 OSC (BMI:30.4±0.5).Measurements:Anthropometric, metabolic and hormonal parameters were determined by anthropometry, enzyme autoanalyzer, immunoassay and enzyme-linked immunosorbent assay.Results:Triglyceride, total cholesterol divided by high-density lipoprotein (HDL) cholesterol (TC/HDL) and leptin levels were significantly higher whereas the HDL and the molar ratio of insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein (IGFBP)-3 levels were significantly lower in both OB and OSC groups than those in the Nor group. Compared to normal subjects, insulin and homeostasis model assessment (HOMA) index levels were significantly higher in OSC, and, in OSC, insulin sensitivity and insulin-like growth factor (IGF)-1 were significantly lower. Although the anthropometric parameters in the OB and OSC groups were similar, in the OSC group the waist-to-hip ratio (WHR), insulin levels and HOMA index were significantly higher, while insulin sensitivity, cholesterol, low-density lipoprotein (LDL) cholesterol, TC/HDL, LDL/HDL, IGF-1 and IGF-1/IGFBP-3 molar ratio were lower, than those of the OB group.Conclusion:Insulin homeostasis and lipid profiles in clozapine-treated schizophrenic obesity were different from those in non-psychiatric obesity with similar anthropometric parameters, body weight and BMI. Among the three groups, the highest fasting insulin, the lowest insulin sensitivity and the highest HOMA index occurred in the OSC group. The OSC group was characterized by impaired glucose–insulin homeostasis, abnormal lipid profiles and hormonal changes in the GH-IGF-IGFBP axis and in leptin.International Journal of Obesity (2008) 32, 436–442; doi:10.1038/sj.ijo.0803750; published online 23 October 2007 [ABSTRACT FROM AUTHOR]

Background:Adult obesity prevalence is influenced by rates of weight gain or loss among individual persons, but few studies have measured individual weight change in large populations. Changes in weight may not coincide with changes in the lipid accumulation product (LAP), a continuous index derived from waist circumference and triglycerides concentration for estimating excess lipids.Design and measurements:Descriptive report of longitudinal changes from US studies that included body mass index (BMI, kg/m2) and LAP.Subjects:A total of 16 763 white and black adults studied between 1989 and 1996 in three observational cohorts (Coronary Artery Risk Development in Young Adults, Atherosclerosis Risk in Communities Study and Cardiovascular Health Study).Results:The means of individual annual changes in BMI were positive for young adults, but the mean changes were reduced at older ages (P for linear trend <0.001), becoming negative after 73–83 years old. These mean, individual changes in BMI, specific to sex and age, were approximately 0.1 U/year greater than those reported from previous, representative, longitudinal measurements collected in the United States between 1971 and 1984. Mean, individual annual changes in LAP were strongly positive before middle age. For men, the annual LAP changes were reduced at older ages (P linear trend <0.05). For women, they were greater at older ages (white women, P<0.001) or remained unchanged (black women, P>0.3). With increasing age, there was a greater proportion of persons whose positive LAP change was accompanied by simultaneous BMI change that was negative or zero.Conclusions:These longitudinal observations made during 1989–1996 suggest greater annual changes in BMI compared to an adult cohort studied during 1971–1984. As estimated by LAP, adults of all ages tended to accumulate excess lipids, including circumstances in which they lost weight.International Journal of Obesity (2008) 32, 136–143; doi:10.1038/sj.ijo.0803697; published online 7 August 2007 [ABSTRACT FROM AUTHOR]

Introduction:Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in common with polycystic ovary syndrome (PCOS) women. Early gestation exposure (E) results in insulin resistance, impaired pancreatic β-cell function and type 2 diabetes, while late gestation exposure (L) results in supranormal insulin sensitivity that declines with increasing body mass index (BMI).Objective:To determine whether PA females have altered body fat distribution.Design:Five early-treated PA (EPA), five late-treated PA (LPA) and five control adult female monkeys underwent somatometrics, dual-X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Five control and five EPA females underwent an intravenous glucose tolerance test to assess the relationship between body composition and glucoregulation.Results:There were no differences in age, weight, BMI or somatometrics. LPA females had ∼20% greater DXA-determined total fat and percent body fat, as well as total and percent abdominal fat than EPA or control females (P0.05). LPA females also had ∼40% more CT-determined non-visceral abdominal fat than EPA or control females (P0.05). The volume of visceral fat was similar among the three groups. EPA (R 2=0.94, P0.01) and LPA (R 2=0.53, P=0.16) females had a positive relationship between visceral fat and BMI, although not significant for LPA females. Conversely, control females had a positive relationship between non-visceral fat and BMI (R 2=0.98, P0.001). There was a positive relationship between basal insulin and total body (R 2=0.95, P0.007), total abdominal (R 2=0.81, P0.04) and visceral (R 2=0.82, P0.03) fat quantities in EPA, but not control females.Conclusions:Prenatal androgenization in female rhesus monkeys induces adiposity-dependent visceral fat accumulation, and late gestation androgenization causes increased total body and non-visceral fat mass. Early gestation androgenization induces visceral fat-dependent hyperinsulinemia. The relationship between the timing of prenatal androgen exposure and body composition phenotypes in this nonhuman primate model for PCOS may provide insight into the heterogeneity of metabolic defects found in PCOS women.International Journal of Obesity (2007) 31, 1579–1585; doi:10.1038/sj.ijo.0803638; published online 1 May 2007 [ABSTRACT FROM AUTHOR]

Objective:To determine whether increased expression of macrophage markers and of inflammatory markers in subcutaneous adipose tissue is associated with liver fat in human obesity. We also determined whether expression of TNF (gene encoding TNF-α), HSD11B1 (gene encoding 11β-HSD-1) and RETN (gene encoding resistin) in cultured monocyte-derived macrophages differs between obese/overweight and non-obese subjects.Design:Cross-sectional comparison of obese/overweight and non-obese subjects with respect to adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity.Subjects:Adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity: 10 healthy non-obese (24.2±1.0 kg/m2) and 10 healthy obese/overweight (33.1±1.7 kg/m2) women. Gene expression in monocyte-derived macrophages: seven healthy non-obese (22.1±0.7 kg/m2) and seven healthy obese/overweight (36.9±2.2 kg/m2) women.Measurements:Adipose tissue biopsies and blood samples for isolation of peripheral mononuclear cells were taken after an overnight fast. Liver fat content was measured using magnetic resonance proton spectroscopy. Whole body insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp technique. Expression levels of TNF, HSD11B1, RETN and the macrophage markers CD68 and ITGAM were determined by real-time PCR.Results:In adipose tissue, expression of HSD11B1, ITGAM and CD68 was significantly increased in the obese/overweight as compared to the non-obese group. Expression of all these genes was closely positively correlated with liver fat content and inversely correlated with whole body insulin sensitivity. The associations between expression of CD68, ITGAM and HSD11B1 and liver fat were independent of obesity. There were no differences in TNF, HSD11B1, RETN or CD68 gene expression basally or after stimulation with lipopolysaccharide in monocyte-derived macrophages between obese/overweight and non-obese subjects.Conclusion:Accumulation of fat in the liver is associated with increased adipose tissue inflammation independent of obesity.International Journal of Obesity (2007) 31, 1617–1625. doi:10.1038/sj.ijo.0803635; published online 24 April 2007 [ABSTRACT FROM AUTHOR]

Objective:Lipodystrophy is the major complication of antiretroviral therapy in HIV-infected patients. Its pathophysiology is not well understood, but has been linked to antiadipogenic effects of antiretroviral drugs. Lipin represents a newly characterized protein that is critical for adipocyte differentiation, and lipin deficiency leads to lipodystrophy in the mouse. The objective of this study was to determine whether altered lipin gene expression is associated with HIV lipodystrophy in humans.Design:We measured lipin mRNA levels in subcutaneous abdominal and femoral-gluteal adipose tissue biopsies from HIV-infected patients with or without lipodystrophy, and in healthy controls. Real-time reverse transcription-PCR was performed to quantitate total lipin expression levels, and expression of two lipin isoforms (lipin-α and -β) that are generated by alternative mRNA splicing.Results:As predicted from studies with mice, lipin mRNA levels were correlated with limb fat mass in HIV patients, with lower lipin levels in patients with lipodystrophy than those without lipodystrophy. Unexpectedly, however, this was explained by an increase in lipin-β expression in HIV patients without lipodystrophy compared to patients with lipodystrophy and control subjects. In addition, lipin expression levels were inversely correlated with adipose tissue expression of inflammatory cytokines interleukin (IL)-6, IL-8 and IL-18, which typically increase in HIV-associated lipoatrophy.Conclusions:Elevated lipin expression levels are associated both with the maintenance of greater fat mass and lower cytokine expression in HIV-infected patients. Based on the demonstrated role for lipin in promoting lipogenic gene expression, these observations raise the possibility that variations in lipin levels may contribute to variations in adipose tissue mass and function that distinguish HIV patients with and without lipodystrophy.International Journal of Obesity (2007) 31, 449–456. doi:10.1038/sj.ijo.0803434; published online 18 July 2006 [ABSTRACT FROM AUTHOR]

Background:Features of the metabolic syndrome comprise a major risk for cardiovascular disease and will increase in prevalence with rising childhood obesity. We sought to identify early life influences on development of obesity, hypertension and dyslipidemia in children.Methods and results:Cluster analysis was used on a subset of a longitudinal Australian birth cohort who had blood samples at age 8 (n=406). A quarter of these 8-year-olds fell into a cluster with higher body mass index, blood pressure (BP), more adverse lipid profile and a trend to higher serum glucose resembling adult metabolic syndrome. There was a U-shaped relationship between percentage of expected birth weight (PEBW) and likelihood of being in the high-risk cluster. The high-risk cluster had elevated BP and weight as early as 1 and 3 years old. Increased likelihood of the high-risk cluster group occurred with greatest weight gain from 1 to 8 years old (odds ratio (OR)=1.4, 95% confidence interval (CI)=1.3–1.5/kg) and if mothers smoked during pregnancy (OR=1.82, CI=1.05–3.2). Risk was lower if children were breast fed for 4 months (OR=0.6, 95% CI=0.37–0.97). Newborns in the upper two quintiles for PEBW born to mothers who smoked throughout pregnancy were at greatest risk (OR=14.0, 95% CI=3.8–51.1) compared to the nadir PEBW quintile of non-smokers.Conclusion:A U-shaped relationship between birth weight and several components of the metabolic syndrome was confirmed in a contemporary, well-nourished Western population of full-term newborns, but post-natal weight gain was the dominant factor associated with the high-risk cluster. There was a prominence of higher as well as lowest birth weights in those at risk. Future health programs should focus on both pre- and post-natal factors (reducing excess childhood weight gain and smoking during pregnancy), and possibly the greatest benefits may arise from targeting the heaviest, as well as lightest newborns, especially with a history of maternal smoking during pregnancy.International Journal of Obesity (2007) 31, 236–244. doi:10.1038/sj.ijo.0803394; published online 23 May 2006 [ABSTRACT FROM AUTHOR]

Objective: To determine the safety and efficacy of a dietary supplement with a low dose of ephedra and caffeine in overweight/ obese premenopausal female subjects. Design: A 9-month, double-blind, randomized control study compared the efficacy and safety of a dietary supplement with ephedra and caffeine to a control supplement. Subjects: Sixty-one healthy, premenopausal women with body mass index (BMI) from 27 to 39 kg/m² were randomly assigned and received a dietary supplement (40 mg/day ephedra alkaloids, 100 mg/day caffeine, high potency mixture of vitamins, minerals, omega-3 fatty acids) or a control supplement for 9 months. Measurements: Efficacy: changes in body weight, body composition, lipids, insulin, leptin, adiponectin, ghrelin, and self-reports of physical activity, diet and quality of life indices. Safety: blood pressure, heart rate, electrocardiograms, urinalysis, blood histology, serum chemistry measures and self-reported symptoms. Results: Forty-one women completed the study. The treatment group lost significantly more body weight (-7.18 kg) and body fat (-5.33 kg) than the control group (-2.25 and -0.99 kg, respectively), and showed significant declines in heart rate, serum cholesterol, triglycerides, cholesterol to high-density lipoprotein ratio, glucose, fasting insulin, and leptin. Blood pressure, electrocardiograms, other clinical chemistry measures, blood histology, urinalysis, and self-reported physical activity were similar in the groups. Minor symptoms included dry mouth, insomnia, nervousness and palpitations. The treatment group reported more energy and decreased appetite compared to controls and scored higher on a quality of life domain assessing vitality. Conclusion: A dietary supplement containing a low potency ephedra/caffeine mixture appeared safe and effective in causing loss of weight and body fat, and improving several metabolic parameters, including insulin sensitivity and lipid profiles when tested under physician supervision. Such supplements could be a useful tool to assist with weight loss. [ABSTRACT FROM AUTHOR]

Objective:The combined effects of limited food intake and OE treatment have been analysed in order to determine whether hypocaloric diets enhance the slimming effects of OE on mature overweight male rats. Two levels of dietary limitation at 50 and 25% of a standard intake were established, roughly corresponding to the human LCDs and VLCDs.Design:Wistar male rats (6 weeks old) were made overweight by a cafeteria diet. After transition to standard diet, they were subjected to food restriction: down to 50 or 25% with respect to the transition period. Half the animals were given daily oral gavages of 10 nmol/g oleoyl-estrone (OE), and the rest received only the vehicle during 10 days.Measurements:Changes in weight and body composition: water, lipid, protein or gross energy were determined by comparing the final pool size with that of day 0, calculated from the initial body weight and the composition of untreated rats. Energy and nitrogen balances were estimated. Plasma levels of metabolites and hormones were also measured.Results:OE induced changes in body composition similar to those elicited by a 50% reduction in food, with massive loss of lipid and energy. OE-treated rats ate less than the controls, but additional effects on body composition on reduced diet were minimal. OE improved metabolic homoeostasis: better maintained glycaemia, lower cholesterol and shallower hormonal changes, but at the expense of slightly increased protein mobilisation.Conclusions:The data presented suggest that no advantages are accomplished by combining OE treatment and hypocaloric diets compared with OE alone, at least under the experimental conditions tested, since the effects were not additive. Despite OE affecting food intake, mechanisms other than that are deemed responsible for the mobilisation of body fat, since intake alone cannot explain the effects on body weight, nor the metabolic and hormonal changes in OE-treated rats. It is concluded that the combination of food restriction and OE may result in unwanted increased protein mobilisation with no synergy between both slimming treatments.International Journal of Obesity (2006) 30, 1149–1156. doi:10.1038/sj.ijo.0803224; published online 17 January 2006 [ABSTRACT FROM AUTHOR]

Objective: Familial combined hyperlipidemia (FCH) is characterized by elevated levels of total cholesterol (TC), triglycerides (TG) and apolipoprotein B (apo B) and is associated with premature cardiovascular disease (CVD). Other features of FCH are obesity and insulin resistance. Serum leptin levels have also been associated with obesity, insulin resistance and atherosclerosis. Leptin exerts its effect through the leptin receptor (LEPR). The aim of this study is to determine whether the Gln223Arg polymorphism in the LEPR gene contributes to FCH and its associated phenotypes.Methods: The study population consists of 37 families, comprising 644 subjects, of whom 158 subjects were diagnosed as FCH. The FCH diagnosis was based on plasma TC and TG levels, adjusted for age and gender, and absolute apo B levels, according to our recently published nomogram. The Gln223Arg polymorphism was studied by restriction fragment length polymorphism-PCR.Results: Carriers of one or two Arg alleles had an increased risk of FCH, compared to subjects homozygous for the Gln allele (OR=1.6 [95% CI 1.0-2.4]). A difference in high-density lipoprotein cholesterol (HDL-c) levels was present between carriers and non-carriers of an Arg allele, 1.21 vs 1.28 mmol/l, respectively (P=0.04), but no differences in obesity, insulin resistance and other lipid parameters were found.Conclusion: The Gln223Arg polymorphism in the LEPR gene is associated with FCH, which is supported by a significant association between HDL-c levels and the LEPR gene. [ABSTRACT FROM AUTHOR]

Objectives:To assess the implications of variation in Metabolic Syndrome (MS) definition (biochemical and anthropometric indicators) on MS prevalence estimates in a population of overweight and mildly obese children.Design:Cross-sectional study.Subjects:Ninety-nine (64 girls) overweight or mildly obese, but otherwise healthy, pre-pubertal 6–9-year olds recruited for a randomized controlled trial of weight management.Measures:Height, weight and waist circumference were measured with BMI and waist z-scores calculated. Fasting cholesterol and fractions, glucose and insulin were measured, together with systolic and diastolic blood pressure (BP). Anthropometric and metabolic indicators were classified as normal or elevated using adult- or child-specific cut points with clustering of MS indicators also assessed using two adult and three child-specific definitions.Results:A total of 0–4% of subjects were classified with MS when adult definitions were applied. This increased to between 39 and 60% using child-specific definitions, varying according to whether hyperinsulinaemia was central to the MS classification. Systolic BP, triglycerides, total cholesterol, high-density lipoprotein cholesterol and waist z-score increased across insulin quartiles (P<0.05). The use of body mass index and waist circumference in the MS definition classified the same subjects.Conclusions:The classification of MS in children depends strongly on the definition chosen, with MS prevalence estimates higher if insulin is part of the definition and child-specific cut points for metabolic indicators are used. Hyperinsulinaemia and MS are common consequences of childhood obesity but they are not commonly part of the assessment or management plan for weight management in children. There is a need for the establishment of normal insulin ranges and consistent definition of MS in childhood and adolescence.International Journal of Obesity (2006) 30, 853–860. doi:10.1038/sj.ijo.0803195; published online 10 January 2006 [ABSTRACT FROM AUTHOR]

Objective:We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring.Design:Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation. The macrosomic (MAC) pups were killed at the age of 60 and 90 days.Measurements:Lipid peroxidation was measured as the concentrations of plasma thiobarbituric acid reactive substances (TBARS), and the total antioxidant status was determined by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma vitamin A, E and C concentrations, and (iii) antioxidant enzymes activities in erythrocytes. The plasma lipid concentrations and fatty acid composition were also determined.Results:Diabetes increased plasma triglyceride and cholesterol concentrations, whereas macrosomia was associated with enhanced plasma cholesterol and triglyceride levels, which diminished by feeding n-3 PUFA diet. N-3 PUFA diet also reduced increased plasma TBARS and corrected the decreased ORAC values in diabetic rats and their macrosomic offspring. EPAX diet increased the diminished vitamin A levels in diabetic mothers and vitamin C concentrations in macrosomic pups. Also, this diet improved the decreased erythrocyte superoxide dismutase and glutathione peroxidase activities in diabetic and macrosomic animals.Conclusion:Diabetes and macrosomia were associated with altered lipid metabolism, antioxidant enzyme activities and vitamin concentrations. N-3 PUFA diet improved hyperlipidemia and restored antioxidant status in diabetic dams and MAC offspring.International Journal of Obesity (2006) 30, 739–750. doi:10.1038/sj.ijo.0803211; published online 17 January 2006 [ABSTRACT FROM AUTHOR]

Objective:To compare the value of body fat mass (%FM) to indirect measures of general (body mass index (BMI)) and central adiposity (waist circumference (WC); waist-to-height ratio (WC/ht)) for the prediction of overweight- and obesity-related metabolic risk in a study population with a high prevalence of metabolic syndrome (MSX).Methods:BMI, WC, WC/ht, body composition (by air-displacement plethysmography) and metabolic risk factors: triglycerides, cholesterol, HDL-cholesterol (HDL-C), uric acid, systolic blood pressure (BPsys), insulin resistance by homeostasis model assessment (HOMA-IR) and C-reactive protein (CRP) were measured in 335 adults (191 women, 144 men; mean age 53 ±13.9 years, prevalence of MSX 30%).Results:When compared with BMI and WC, %FM showed weaker associations with metabolic risk factors, except for CRP and BPsys in men. In women, HDL-C and HOMA-IR showed the closest correlations with BMI. For all other risk factors, WC or WC/ht were the best predictors in both sexes. Differences in the strength of correlations between an obesity index and different risk factors exceeded the differences observed between all obesity indices within one risk factor. In stepwise multiple regression analyses, WC/ht was the main predictor of metabolic risk in both sexes combined. However, analysis of the area under receiver operating characteristic curves for prediction of the prevalence of 2 component traits of the MSX revealed a similar accuracy of all obesity indices.Conclusions:At the population level, measurement of body FM has no advantage over BMI and WC in the prediction of obesity-related metabolic risk. Although measures of central adiposity (WC, WC/ht) tended to show closer associations with risk factors than measures of general adiposity, the differences were small and depended on the type of risk factor and sex, suggesting an equivalent value of methods.International Journal of Obesity (2006) 30, 475–483. doi:10.1038/sj.ijo.0803144; published online 1 November 2005 [ABSTRACT FROM AUTHOR]

Objective:The purpose of this study was to determine the relationships between adipocyte hormones acylation stimulating protein (ASP), adiponectin, complement C3 (C3) (ASP precursor) and insulin, C-reactive protein (CRP), lipid profiles and insulin resistance in lean vs obese type 2 diabetes subjects.Subjects:Lean type 2 diabetes subjects (DL n=27) vs obese type 2 diabetes subjects (DO n=55) were compared to age-matched nondiabetic groups (Obese, OB n=55 and control, CTL n=50).Results:The DO group demonstrated significant increases in plasma ASP and C3 with decreases in plasma adiponectin as compared to CTL. Interestingly, these increases in ASP and C3 were as high, or greater, in the DL group in spite of normal weight. By contrast adiponectin in the DL group was comparable to CTL, in spite of marked insulin resistance. C3 correlated with insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR); ASP correlated with body mass index (BMI), glucose, insulin and plasma lipid parameters (non-esterified fatty acids (NEFA), triglyceride, cholesterol and apolipoprotein B). Adiponectin correlated with BMI, glucose, NEFA, triglyceride, high-density lipoprotein cholesterol and apolipoprotein A1 but not HOMA-IR, ASP or C3. CRP correlated only with HOMA-IR.Conclusion:Increased ASP and C3 are both associated with diabetes and related lipid factors but are not regulated coordinately. Adiponectin appears to be more closely related to body size (decreased in obese subjects) than insulin resistance in these subjects.International Journal of Obesity (2006) 30, 439–446. doi:10.1038/sj.ijo.0803173; published online 22 November 2005 [ABSTRACT FROM AUTHOR]

Objective:Oxidative stress may be the unifying mechanism underlying the development of comorbidities in obesity. Evidence suggests that a clustering of sources of oxidative stress exists in obesity: hyperglycemia, hyperleptinemia, increased tissue lipid levels, inadequate antioxidant defenses, increased rates of free radical formation, enzymatic sources within the endothelium, and chronic inflammation.Method:This review provides a summary of the available evidence on systemic oxidative stress in humans and specific metabolic pathways by which obesity may elevate systemic oxidant stress. The authors suggest possible methods of reducing oxidative stress such as antioxidant supplementation, caloric restriction and/or physical activity and surgical intervention to combat free radicals and reduce adipose tissue.Results:Obesity is associated with oxidative stress and can be reduced with weight loss (regardless of exercise or surgery induced weight loss), caloric restriction or antioxidant rich diets.Conclusion:Oxidative stress levels are elevated in human obesity, and these levels are modifiable with various lifestyle modifications and surgical interventions.International Journal of Obesity (2006) 30, 400–418. doi:10.1038/sj.ijo.0803177; published online 22 November 2005 [ABSTRACT FROM AUTHOR]

Introduction:Although lipid profiles tend to worsen with age, it is not fully known if such age-related changes are influenced primarily by body composition and lifestyle or by other aspects of aging.Objective:We investigated the extent to which the fat and fat-free components of body mass index (BMI) and lifestyle factors influence patterns of change in lipids independent of age.Design:Serial data were analyzed using sex-specific longitudinal models. These models use serial data from individuals to assume a general pattern of change over time, while allowing baseline age and the rate of change to vary among individuals.Subjects:Serial data were obtained from 940 examinations of 269 healthy white participants (126 men, 143 women), aged 40–60 years, in the Fels Longitudinal Study.Measurements:Measurements included age, the fat (FMI) and fat-free mass (FFMI) components of BMI, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), triglycerides (TG), total cholesterol (TC), fasting glucose and insulin, physical activity, alcohol use and smoking, and women's menopausal status and estrogen use.Results:In both sexes, increased FMI was significantly associated with increased LDL-C, TG and TC, and decreased HDL-C. Increased FFMI was significantly related to decreased HDL-C and increased TG. Independent age effects remained significant only for LDL-C and TC in men and TC in women. Increased insulin was significantly related to increased TG in women. Moderate alcohol consumption was associated with higher HDL-C in men. Physical activity lowered male LDL-C and TC levels, and increased female HDL-C levels. Menopause was associated with increases in LDL-C. Premenopausal women not using estrogen had significantly lower HDL-C, TG, and TC than postmenopausal women taking estrogen.Conclusions:(1) Age is an important independent predictor for LDL-C and TC in men, and TC in women, but it is not as influential as body composition and lifestyle on HDL-C and TG in men and women, and LDL-C in women. (2) Increasing FMI is the major contributor to elevated TC, LDL-C and TG levels, and decreased HDL-C levels in men and women. (3) FFMI significantly influences HDL and TG levels in both sexes. (4) Maintaining a lower BMI via a reduced fat component may be more beneficial in lowering CVD risks than other factors.International Journal of Obesity (2006) 30, 251–260. doi:10.1038/sj.ijo.0803129; published online 25 October 2005 [ABSTRACT FROM AUTHOR]

OBJECTIVE:To investigate changes in adipocyte hormones and lipid oxidation during and after a weight-reduction programme in severely obese adolescents.DESIGN:Longitudinal-clinical investigation including a 9-month multidisciplinary weight-reduction programme in a specialised institution with lifestyle education, moderate energy restriction and regular physical activity, followed by a 4-month period at home.SUBJECTS:A total of 26 (12 boys and 14 girls) severely obese adolescents (mean BMI: 33.9 kg/m2; 41.5% fat mass (FM)).MEASUREMENTS:Before starting (M0), at the end (M9), and 4 months after the end (M13) of the intervention blood samples were collected at fast, body composition was assessed by dual X-ray absorptiometry, and energy expenditure (EE) and substrate oxidation were assessed by whole-body indirect calorimetry over 24 h.RESULTS:At M9, adolescents had lost 19.0% body weight (BW), 41.3% FM (P<0.001), with a minor fat free mass (FFM) loss in girls (6.4%, P<0.001) but no significant FFM changes in boys. Plasma leptin concentration at M9 was 70% lower (P<0.001), whereas plasma adiponectin concentration was 26.6% higher (P<0.001). The results also suggest that after adjustment for FFM and energy balance, sleeping and sedentary activity lipid oxidation rates were higher at M9 than at M0. At M13, plasma adiponectin, insulin, glucose and LDL concentrations returned to the initial levels, and leptin to an intermediate level in the 10 adolescents who had regained BW. Adjusted lipid oxidation rate decreased in both groups of subjects but it was not correlated to any change in plasma adipocyte hormones, which rather changed in relation to FM modifications.CONCLUSION:Moderate energy restriction and regular moderate and high intensity physical activities in obese adolescents induced beneficial changes in BW and composition, lipid oxidation and blood parameters, especially adipocyte hormones.International Journal of Obesity (2005) 29, 1184–1191. doi:10.1038/sj.ijo.0802977 [ABSTRACT FROM AUTHOR]

Objective: To investigate whether low-carbohydrate diets are efficient for reduction of body weight and through which mechanism.Design: A couple of studies using low-carbohydrate diets in the treatment of obesity are reviewed. Mechanisms for explaining the reduced appetite are described in relation to knowledge on regulation of appetite for fat and carbohydrate.Results: Studies with low-carbohydrate diets demonstrate a rapid weight loss, being more pronounced after 3 and 6 months compared to low-fat diets. After 12 months there is no difference between the low-carbohydrate and the conventional low-fat diet on weight loss. Both diets lead to improvements in risk factors for coronary heart disease, the low-carbohydrate diet leading to a greater decrease in serum triglycerides and increase in HDL cholesterol compared to the low-fat diet. Blood pressure, insulin sensitivity and LDL cholesterol were improved to a similar degree by the two diets. The mechanism for the rapid weight loss with the low-carbohydrate diet is a suppressed appetite, first through the high-protein content of the diet, second through the ketogenic nature of the diet with satiety signals for fat being active and third through the absence of hunger-promoting carbohydrate components like sucrose and/or fructose.Conclusion: A rapid initial weight loss occurs with a low-carbohydrate diet due to a suppressed appetite. There is as yet no indication of an increased metabolic rate and an increased thermogenesis by the low-carbohydrate diet. The safety and efficacy of low-carbohydrate diets have to await further studies. [ABSTRACT FROM AUTHOR]

Objectives: This paper aim to review the newest literature linking physical inactivity and low fitness to metabolic disorders including cardiovascular disease (CVD) risk factors and obesity.Methods: There is a rationale for early prevention of CVD if (a) children have a risk factor profile, where risk for future disease is increased, (b) physical activity and CVD risk factors track into adulthood, and (c) increased physical activity can improve the risk factor profile. We reviewed the evidence for a progressive evolution of atherosclerosis starting in childhood, and also that physical activity decreases the rate of the process through several mechanisms. Among the central mechanisms mediating the effect of physical activity are (a) increased insulin sensitivity, (b) a non-insulin-dependent glucose uptake, which causes lower insulin release, (c) an improved ratio between HDL and LDL cholesterol because of increased activity of lipoprotein lipase, and d) improved function of other metabolic hormones and enzymes for fat metabolism.Results: The association between CVD risk factors and physical activity/fitness is weak, when risk factors are analysed isolated. In the normal healthy population of children, studies have shown that risk factors cluster and this clustering is strongly related to low physical activity or fitness. In European children it has been found that as many as 15% of 9-y-old children has clustered risk. Most of the overweight and obese children are among these, but many of the children are lean inactive children, who may later become overweight because of insulin resistance.Conclusion: It can be concluded that there is a large potential for primary prevention of CVD in European children, and lifestyle changes including increased physical activity as one of the key actions should be initiated. [ABSTRACT FROM AUTHOR]

PURPOSE:The purpose of this study was to examine the association of body mass index (BMI) and aerobic fitness on cardiovascular disease (CVD) risk factors in adolescents.METHODS:The sample included 416 boys and 345 girls 9–18 y of age from the Québec Family Study. Participants were cross-tabulated into four groups using a median split of age-adjusted physical working capacity (PWC) and body mass index (BMI). Group differences in age-adjusted CVD risk factors (blood pressures, fasting total cholesterol (CHOL), LDL -C, HDL-C, HDL/CHOL, triglycerides, glucose, and a composite risk factor score) were examined by two-way ANOVA.RESULTS:Several CVD risk factors showed significant main effects for PWC, BMI and/or the PWC by BMI interaction. In general, low fit males and females had higher blood lipids and glucose compared to their high fit counterparts within BMI categories although none of the differences reached statistical significance. The high fit/low BMI group showed the best CVD risk factor profile while the low fit/high BMI showed a poorer profile as evidenced by several significant differences between these two groups. Other significant differences occurred for various risk factors between groups.CONCLUSION:Both aerobic fitness and BMI show an independent association with CVD risk factors in adolescents.International Journal of Obesity (2005) 29, 1077–1083. doi:10.1038/sj.ijo.0802995; published online 24 May 2005 [ABSTRACT FROM AUTHOR]

Objective: Use the meta-analytic approach to examine the effects of aerobic exercise on lipids and lipoproteins in overweight and obese adults.Data Sources: (1) Computerized literature searches, (2) cross-referencing from review and original articles, (3) hand searching, and (4) expert review of reference list.Study Selection: (1) randomized controlled trials, (2) aerobic exercise > or =8 weeks, (3) adult humans > or =18 y of age, (4) all subjects overweight or obese (BMI > or =25 kg/m(2)), (5) studies published in journal, dissertation, or master's thesis format, (6) studies published in the English-language, (7) studies published between 1 January 1955 and 1 January 2003, (8) assessment of one or more of the following lipid and/or lipoprotein variables: total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG).Data Abstraction: Dual-coding by the first two authors (inter-rater agreement=0.96).Results: In total, 13 studies representing 31 groups (17 exercise, 14 control), 613 subjects (348 exercise, 265 control), and up to 17 outcomes were available for pooling. Across all categories, random-effects modeling resulted in statistically significant improvements for TC (X +/- s.e.m., - 3.4+/-1.7 mg/dl, 95% CI, - 6.7 to - 0.2 mg/dl) and TG (X +/-s.e.m., - 16.1+/-7.3 mg/dl, 95% CI, - 30.2 to - 2.1 mg/dl) but not HDL (X +/- s.e.m., 1.6+/-0.8 mg/dl, 95% CI, - 0.02 to 3.2 mg/dl) or LDL (X +/-s.e.m., - 0.5+/-1.3 mg/dl, 95% CI, - 3.0 to 2.0 mg/dl). Changes were equivalent to improvements of 2% (TC), 11% (TG), 3% (HDL), and 0.3% (LDL). After conducting sensitivity analyses (each study deleted from the model once), only decreases in TG remained statistically significant. Increases in HDL were associated with increases in maximum oxygen consumption (VO(2 max) in ml/kg/min, r=0.75, P=0.002) and decreases in body weight (r=0.77, P<0.001), while decreases in LDL were associated with decreases in body weight (r=0.75, P=0.009).Conclusions: Aerobic exercise decreases TG in overweight and obese adults. However, a need exists for additional randomized controlled trials in various overweight and/or obese populations above and beyond those included in our analysis. [ABSTRACT FROM AUTHOR]

OBJECTIVES:: To examine differences in the relationship between fat distribution and lipid coronary risk factors in Caucasian and Japanese population and further to determine whether the cut-points for body mass index (BMI) and waist circumference (WC) proposed by WHO and NHLBI are applicable to Japanese population as a predictor of a lipid risk factor abnormality or not. RESEARCH METHODS AND PROCEDURES:: Subjects were 895 participants of the Baltimore Longitudinal Study of Aging in the US (BLSA) and 1705 participants of the Longitudinal Study of Aging by the National Institutes for Longevity Science in Japan (NILS-LSA). Subjects were divided into four demographic groups as younger (age<65?y) men and women, and older (age=65?y) men and women. Blood total cholesterol, triglycerides, LDL- and HDL-cholesterol and anthropometry were measured. Regression coefficients of BMI and WC on risk factors, sensitivity and specificity of the BMI and WC cut-points for blood lipid abnormality, and mean values of blood lipids at BMI or WC cut-points were computed in both populations. RESULTS:: Height, weight, WC and BMI were significantly greater in the BLSA than those in the NILS-LSA subjects. Total cholesterol, HDL- and LDL-cholesterol were significantly greater in the NILS-LSA than in the BLSA subjects. Sensitivities of BMI and WC cut-points were much lower in the NILS-LSA than in the BLSA subjects. Specificities of BMI and WC cut-points were higher in the NILS-LSA than in the BLSA subjects. Mean values of triglycerides, total cholesterol, HDL- and LDL-cholesterol at BMI=25 were significantly greater in the NILS-LSA than in the BLSA subjects. At the WC cut-point (94?cm for men, 80?cm for women), mean values of all lipids were significantly greater in the NILS-LSA than in the BLSA subjects with the exception of triglycerides in younger women. CONCLUSIONS:: The Japanese subjects have smaller BMI and WC, worse total and LDL-cholesterol levels and better HDL-cholesterol levels compared to Caucasians. Sensitivities of BMI and WC for predicting lipid risk factor abnormality are much lower in Japanese. The cut-points for BMI and WC proposed by WHO and NHLBI may be too high for predicting an abnormality in triglycerides, total and LDL-cholesterol in Japanese. For detecting an abnormal HDL-cholesterol level, the BMI and WC cut-points may not be as beneficial for the Japanese population as for Caucasians.International Journal of Obesity (2005) 29, 228-235. doi:10.1038/sj.ijo.0802615 Published online 30 November 2004 [ABSTRACT FROM AUTHOR]