ACDC/Adiponectin and PPAR‐γ Gene Polymorphisms: Implications for Features of Obesity

Objective: The main purpose of this study was to investigate associations of single‐nucleotide polymorphisms (SNPs) in the adipocyte C1q and collagen domain‐containing (ACDC) gene and its regulator, the nuclear peroxisome proliferator‐activated receptor (PPAR)‐γ gene, with body fat mass and its topographical distribution in postmenopausal women. Research Methods and Procedures: Participants were 1501 healthy women, 60 to 85 years old, who were genotyped for four SNPs in the ACDC gene (−11391G/A, −11377C/G, +45T/G, +276G/T) and the Pro12Ala SNP in the PPAR‐γ gene. Total body fat mass and the central to peripheral fat mass ratio (CFM/PFM ratio) were measured using DXA. Adiponectin and homeostasis model assessment of insulin resistance were measured in 287 subjects. Results: The −11377C/G SNP was associated with adiponectin (p < 0.001) and the CFM/PFM ratio (p = 0.005); the G allele being associated with low adiponectin and high CFM/PFM ratio. Similar associations of adiponectin (p = 0.0001) and the CFM/PFM ratio (p = 0.002) characterized the 1_2 (G_G) promoter haplotype (11391G/A_−11377C/G). Genotype variation of SNP Pro12Ala was associated with total body fat mass (p = 0.04); women with GG being the most obese (p = 0.01). The Ala/Ala (GG) genotype of Pro12Ala SNP interacted with the CC genotype of SNP‐11377C/G in the determination of BMI (p = 0.001), when analyzed using a codominant model. Discussion: Polymorphisms in the ACDC gene are associated with body fat distribution, whereas the Pro12Ala polymorphism in PPAR‐γ is associated with overall adiposity, apparently in interaction with an ACDC promoter SNP.     

Effects of β2‐Adrenergic Receptor Gene Variants on Adiposity: The HERITAGE Family Study

We investigated whether the Arg16Gly and Gln27Glu polymorphisms of the β2‐adrenergic receptor gene were associated with body‐fat and fat‐distribution phenotypes measured before and in response to a 20‐week endurance‐training program. BMI, fat mass (FAT), percentage of body fat (%FAT), sum of eight skinfolds (SF8), and abdominal fat areas assessed by computed tomography were measured in adult sedentary white and black participants of the HERITAGE Family Study. Evidence of gene‐by‐obesity interaction was found in whites for several adiposity phenotypes measured before training. Analyses performed separately in nonobese and obese subjects revealed that obese men carrying the Glu27 allele have lower fat accumulation (BMI, FAT, and %FAT) than noncarriers. Among white obese women, Gly16Gly homozygotes had a lower fat accumulation (BMI, FAT, and SF8) than Arg16Gly and Arg16Arg carriers. In response to endurance training, white women with the Arg16Arg genotype exhibited a greater reduction in BMI, FAT, and %FAT. Results observed in blacks were mostly negative. These results suggest that polymorphisms in the β2‐adrenergic receptor gene influence the amount of body fat in white obese men (Gln27Glu) and women (Arg16Gly), as well as the changes in adiposity in response to endurance training in white women (Arg16Gly).     

Effects of Exercise on Metabolic Risk Variables in Overweight Postmenopausal Women: A Randomized Clinical Trial

Objective: This study examined the effects of exercise on metabolic risk variables insulin, leptin, glucose, and triglycerides in overweight/obese postmenopausal women. Research Methods and Procedures: Sedentary women (n = 173) who were overweight or obese (BMI ≥ 25 kg/m² or ≥24 kg/m² with ≥33% body fat), 50 to 75 years of age, were randomized to 12 months of exercise (≥45 minutes of moderate‐intensity aerobic activity 5 d/wk) or to a stretching control group. Body composition (DXA) and visceral adiposity (computed tomography) were measured at baseline and 12 months. Insulin, glucose, triglycerides, and leptin were measured at baseline and 3 and 12 months. Insulin resistance was evaluated by the homeostasis model assessment formula. Differences from baseline to follow‐up were calculated and compared across groups. Results: Exercisers had a 4% decrease and controls had a 12% increase in insulin concentrations from baseline to 12 months (p = 0.0002). Over the same 12‐month period, leptin concentrations decreased by 7% among exercisers compared with remaining constant among controls (p = 0.03). Homeostasis model assessment scores decreased by 2% among exercisers and increased 14% among controls from baseline to 12 months (p = 0.0005). The exercise effect on insulin was modified by changes in total fat mass (trend, p = 0.03), such that the exercise intervention abolished increases in insulin concentrations associated with gains in total fat mass. Discussion: Regular moderate‐intensity exercise can be used to improve metabolic risk variables such as insulin and leptin in overweight/obese postmenopausal women. These results are promising for health care providers providing advice to postmenopausal women for lifestyle changes to reduce risk of insulin resistance, coronary heart disease, and diabetes.     

Diet‐induced Obese Mice Are Leptin Insufficient After Weight Reduction

Behavioral therapies aimed at reducing excess body fat result in limited fat loss after dieting. To understand the causes for maintenance of adiposity, high‐fat (HF) diet–induced obese (DIO) mice were switched to a low‐fat chow diet, and the effects of chow on histological and molecular alterations of adipose tissue and metabolic parameters were examined. DIO mice reduced and stabilized their body weights after being switched to chow (HF‐chow), but retained a greater amount of adiposity than chow‐fed mice. Reduction in adipocyte volume, not number, caused a decrease in fat mass. HF‐chow mice showed normalized circulating insulin and leptin levels, improved glucose tolerance, and reduced inflammatory status in white adipose tissue (WAT). Circulating leptin levels corrected for fat mass were lower in HF‐chow mice. Leptin administration was used to test whether reduced leptin level of HF‐chow mice inhibited further fat loss. Leptin treatment led to an additional reduction in adiposity. Finally, HF‐HF mice had lower mRNA levels of β₃ adrenergic receptor (β₃‐AR) in epididymal WAT (EWAT) compared to chow‐fed mice, and diet change led to an increase in the WAT β₃‐AR mRNA levels that were similar to the levels of chow‐fed mice, suggesting an elevation in sympathetic activation of WAT during diet switch relative to HF‐HF mice leading to the reduced leptin level and proinflammatory cytokine content. In summary, HF‐chow mice were resistant to further fat loss due to leptin insufficiency. Diet alteration from HF to low fat improved metabolic state of DIO mice, although their adiposity was defended at a higher level.     

Serum Leptin Concentrations and Weight Gain in Postobese,Postmenopausal Women

Objective : This study was designed to determine if serum leptin concentrations (adjusted for fat mass) after weight loss on a low-calorie diet predict subsequent weight gain. Research Methods and Procedures : Body composition and serum leptin concentrations were determined on 14 moderately obese, postmenopausal, nondiabetic women with a familial predisposition to obesity. Assessments were obtained under tightly controlled metabolic ward conditions of macronutrient intake and weight maintenance both before (obese state) and after a mean weight loss of 12.0 kg to normal body weight (postobese state). Four years later, without intervention, body weight and body composition were reassessed. Results : Weight loss resulted in significant decreases in fat mass (29.7 ± 5.4 vs. 20.3 ± 4.7; kg), body mass index (27.7 ± 1.6 vs. 23.0 ± 1.5; kg/m2), percent body fat (40.7 ± 4.3 vs. 33.1 ± 5.0), and serum leptin concentrations (31.8 ± 16.0 vs. 11.5 ± 5.4; ng/mL). Serum leptin concentrations were positively correlated (p<<0.05) with fat mass in both the obese and postobese states (r = 0.67 and r = 0.56, respectively). However, residual serum leptin concentrations (adjusted for fat mass) in the obese and postobese states were not related to changes in body weight (p<= 0.61 and 0.52), fat mass (p = 0.72 and 0.42), body mass index (p = 0.59 and 0.33), or percent body fat (p = 0.84 and 0.46) over the follow-up period. Discussion : These finding do not support the hypothesis that relatively low concentrations of leptin predict weight regain after weight loss. However, because the number of subjects in this study was limited, further studies are warranted.     

Leptin Responses to Weight Loss in Postmenopausal Women: Relationship to Sex‐Hormone Binding Globulin and Visceral Obesity

Objective: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women. Research Methods and Procedures: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone‐binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0 ± 4.5 kg/m²; mean ± SD), women (60 ± 6 years) before and after a 6‐month hypocaloric diet (250 to 350 kcal/day deficit). Results: Body weight decreased by 5.8 ± 3.4 kg (7.1%) and leptin levels decreased by 6.6 ± 11.9 ng/mL (14.5%) after the 6‐month treatment. Insulin levels decreased 10% (p < 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p < 0.0001), fat mass (r = 0.38, p < 0.01), subcutaneous fat area (r = 0.52, p < 0.0001), and with baseline values of SHBG (r = 0.38, p < 0.01) and baseline intra‐abdominal fat area (r = ?0.27, p < 0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r² = 0.24, p < 0.01), relative changes in body weight (cumulative r² = 0.40, p < 0.05), and baseline intra‐abdominal fat area (cumulative r² = 0.48, p < 0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance. Discussion: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.     

Leptin Levels Are Associated with Fat Oxidation and Dietary‐Induced Weight Loss in Obesity

Objective: To examine the relationship between fasting plasma leptin and 24‐hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate oxidations, and SPA as predictive markers of success during a standardized weight loss intervention. Research Methods and Procedures: Twenty‐one nondiabetic obese (body mass index: 33.9 to 43.8 kg/m²) and 13 lean (body mass index: 20.4 to 24.7 kg/m²) men matched for age and height were included in the study. All obese subjects were reexamined after a mean weight loss of 19.2 kg (95% confidence interval: 15.1–23.4 kg) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. Twenty‐four‐hour EE and substrate oxidations were measured by whole‐body indirect calorimetry. SPA was assessed by microwave radar. Results: In lean subjects, leptin adjusted for fat mass (FM) was correlated to 24‐hour EE before (r = ?0.56, p < 0.05) but not after adjustment for fat free mass. In obese subjects, leptin correlated inversely with 24‐hour and resting nonprotein respiratory quotient (r = ?0.47, p < 0.05 and r = ?0.50, p < 0.05) both before and after adjustments for energy balance. Baseline plasma leptin concentration, adjusted for differences in FM, was inversely related to the size of weight loss after 8 weeks (r = ?0.41, p = 0.07), 16 weeks (r = ?0.51, p < 0.05), and 24 weeks (r = ?0.50, p < 0.05). Discussion: The present study suggests that leptin may have a stimulating effect on fat oxidation in obese subjects. A low leptin level for a given FM was associated with a greater weight loss, suggesting that obese subjects with greater leptin sensitivities are more successful in reducing weight.     

Protein Tyrosine Phosphatase 1B Variant Associated with Fat Distribution and Insulin Metabolism

Protein tyrosine phosphatase 1B (PTPN1) affects the regulation of insulin signaling and energy metabolism. We studied whether polymorphisms in the PTPN1 gene impact body fat distribution in the HERITAGE Family Study cohort in 502 white and 276 black subjects. Insulin sensitivity index, glucose disappearance index, acute insulin response to glucose (AIR_glucose), and the disposition index (DI) were obtained from the frequently sampled intravenous glucose tolerance test. White subjects with the G82G at the PTPN1 IVS6+G82A polymorphism had higher body fat levels (p = 0.031) and sum of eight skinfolds (p = 0.003) and highest subcutaneous fat on the limbs (p = 0.002). G82A subjects had the lowest AIR_glucose (p = 0.005) and disposition index (p = 0.040). Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIR_glucose (p from 0.006 to 0.010). The variant PTPN1 Pro387Leu was associated with lower fasting insulin level (p = 0.035) and glucose disappearance index (p = 0.038). In summary, PTPN1 IVS6+G82G homozygotes showed higher levels of all measures of adiposity. G82 allele heterozygotes are potentially at higher risk for type 2 diabetes. Gene‐gene interactions between the PTPN1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity. The PTPN1 Pro387Leu variant was associated with lower glucose tolerance.     

Visceral adiposity is associated with serum retinol binding protein-4 levels in healthy women

Objective: Retinol binding protein‐4 (RBP4) has been reported to impair insulin sensitivity throughout the body. We investigated the relationship between serum RBP4 levels and adiposity indices as well as metabolic risk variables. Research Methods and Procedure: We recruited a total of 102 healthy women 21 to 67 years old. We assessed body composition by computed tomography and divided the study population into four groups based on body weight and visceral fat area (non‐obese without visceral adiposity, non‐obese with visceral adiposity, obese without visceral adiposity, and obese with visceral adiposity). Serum RBP4 levels were measured by radioimmunoassay. Results: Despite similar levels of total body fat, non‐obese women had lower systolic blood pressure, total cholesterol, triglyceride (TG), low‐density lipoprotein (LDL)‐cholesterol levels, insulin resistance indices, and RBP4 levels than non‐obese women with visceral adiposity and had higher high‐density lipoprotein‐cholesterol levels. Similarly, obese women without visceral adiposity had lower blood pressure, total cholesterol, TG levels, insulin resistance indices, and RBP4 levels than obese women with visceral adiposity. In addition, despite having increased body fat, obese women without visceral adiposity had lower TGs, insulin resistance indices, and serum RBP4 levels than non‐obese women with visceral adiposity. By step‐wise multiple regression analysis, visceral fat areas and LDL‐cholesterol levels independently affected RBP4 levels. Discussion: We determined that serum RBP4 levels are independently associated with visceral fat and LDL‐cholesterol levels. These results suggest that, irrespective of body weight, visceral obesity is an independent predictor of serum RBP4 levels, and RBP4 may represent a link between visceral obesity and cardiovascular disease.     

Regulation of Lipolysis and Lipoprotein Lipase after Weight Loss in Obese,Postmenopausal Women

Objective: To test the hypothesis that the greater β‐adrenoceptor (β‐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 β‐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. β‐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.     

Association between Serum Leptin Levels and 24‐Hour Blood Pressure in Obese Women

Objective: To assess the relationship between serum leptin and 24‐hour blood pressure (BP) in obese women, according to body fat distribution. Research Methods and Procedures: A cross‐sectional study was carried out in a population of 70 nondiabetic, normotensive, obese women (40 with android and 30 with gynoid type of obesity) and 20 nonobese healthy women as a control group. All subjects underwent 24‐hour ambulatory BP monitoring. Blood samples were collected for serum leptin and plasma insulin measurements. Total cholesterol and high‐density lipoprotein cholesterol were also measured. Results: Serum leptin levels were significantly higher in obese subjects than in controls, and they were more elevated in android obese women than in gynoid ones. Leptin levels were positively related to body mass index (BMI), insulin, and waist and hip circumferences in the android group. Among gynoid subjects, leptin levels showed positive associations with BMI and insulin. In women with android obesity, strong positive correlations (p < 0.001) were found between leptin levels and 24‐hour systolic BP (SBP), daytime SBP, nighttime SBP, 24‐hour diastolic BP (DBP), and daytime DBP. Multiple regression analyses, including age, insulin and leptin concentrations, BMI, and waist and hip circumferences on 24‐hour and daytime SBP and DBP, showed that only leptin levels contributed to the variability of BP. Conclusions: Our study shows that serum leptin levels are directly related to 24‐hour BP levels in normotensive women with android fat distribution, independently of BMI.     

BMI Is the Main Determinant of the Circulating Leptin in Women after Vertical Banded Gastroplasty

Objective: To assess the main determinant of serum leptin concentration changes in morbidly obese patients treated by banded vertical gastroplasty. Research Methods and Procedures: Serum leptin and insulin concentrations, insulin resistance, BMI, body weight, and body fat mass in 18 obese women and 8 obese men treated by vertical banded gastroplasty were studied. Lean women and men subjects were used as controls. Results: Before surgery, serum leptin and insulin concentrations and insulin resistance index were significantly higher in morbidly obese patients than in control subjects. BMI, body fat mass, and serum triacylglycerol concentrations were also significantly higher in obese than in lean subjects. All of these parameters gradually decreased during 50 weeks after surgery. Univariate regression analysis displayed significant correlations between the following: serum leptin concentration and BMI (and body fat mass), serum leptin concentration and serum insulin concentration, and serum leptin concentration and insulin resistance index. Multivariate regression analysis indicated that only BMI was independently correlated with the decrease in serum leptin concentration. Discussion: Obtained data suggest the following: 1) vertical banded gastroplasty causes reduction of body weight, serum leptin and insulin concentration, insulin resistance, and serum triacylglycerol concentration; and 2) BMI is the main determinant of the circulating leptin concentration in morbidly obese women after anti‐obesity surgery.     

Racial Differences in Adipocyte Size and Relationship to the Metabolic Syndrome in Obese Women

Objective: To determine whether racial differences exist in the relationship of the abnormalities defining the metabolic syndrome (MS) to regional adiposity and fat cell size (FCS) in obese postmenopausal women. Research Methods and Procedures: We determined the relationship of metabolic variables associated with the MS to regional body composition and abdominal (ABD) and gluteal (GLT) FCS in 25 white (CAU) and 25 African‐American (AF‐AMER) older women matched for age (58 ± 5 years; mean ± SD) and BMI (35 ± 4 kg/m²). Results: MS was present in 36% of the AF‐AMER and 57% of the CAU women. There were no differences in total body, trunk, gluteofemoral fat mass or regional FCS, but AF‐AMER women had 22% lower visceral fat, 24% higher insulin, and 31% lower triglyceride levels than CAU women (p < 0.05). Multiple regression analysis with body fat, visceral ABD fat area, and FCS as independent variables showed that GLT FCS was independently correlated with 2‐hour insulin (r = 0.56), triglyceride (r = 0.62), and high‐density lipoprotein cholesterol (r = ?0.72) levels in AF‐AMER women but not in CAU women, where only systolic blood pressure correlated with subcutaneous ABD fat area (r = 0.57) (p < 0.05). Discussion: The associations between GLT FCS and metabolic dysfunction in obese AF‐AMER but not CAU women suggest that central obesity is a less valid predictor of the MS in obese postmenopausal AF‐AMER women than in CAU women and that GLT FCS may be a more sensitive indicator of risk for the MS in AF‐AMER women.     

Low Plasma Leptin Concentration and Low Rates of Fat Oxidation in Weight‐Stable Post‐Obese Subjects

Objective: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post‐obese adults (2 males and 6 females; 48.9 ± 12.2 years; body mass index [BMI]: 24.5 ± 1.0 kg/m²; body fat 33 ± 5%; mean ± SD) who lost 27.1 ± 21.3 kg (16 to 79 kg) and had maintained this weight loss for ≥2 months (2 to 9 months) to eight age‐ and BMI‐matched control never‐obese subjects (1 male and 7 females; 49.1 ± 5.2 years; BMI 24.4 ± 1.0 kg/m²; body fat 33 ± 7%). Research Methods and Procedures: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10‐hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48‐hour period in free living conditions. Results: After adjustment for fat mass and fat‐free mass, post‐obese subjects had, compared with controls, similar levels of physical activity (4185 ± 205 vs. 4295 ± 204 counts) and similar RMR (1383 ± 268 vs. 1430 ± 104 kcal/day) but higher RQ (0.86 ± 0.04 vs. 0.81 ± 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat‐free mass, was lower in post‐obese than in control subjects (4.5 ± 2.1 vs. 11.6 ± 7.9 ng/mL, p < 0.05). Discussion: The low fat oxidation and low plasma leptin concentrations observed in post‐obese individuals may, in part, explain their propensity to relapse.     

Plasma Leptin Response to an Epinephrine Infusion in Lean and Obese Women

Objective: Because leptin production by adipose tissue is under hormonal control, we examined the impact of epinephrine administration on plasma leptin concentrations. Research Methods and Procedures: We measured plasma leptin, insulin, and free fatty acid (FFA) responses after a 60-minute epinephrine infusion (0.010 μg/kg fat free mass/min) followed by a 30-minute recovery period (no infusion) in a group of 11 lean (mean body mass index ± SD: 22.6 ± 1.1 kg/m²) and 15 obese (30.0 ± 1.3 kg/m²) premenopausal women. Leptin, insulin, and FFA levels were measured in plasma before (−15 and 0 minutes) and at every 30 minutes over the 90-minute period. Results: In both lean and obese individuals, plasma leptin was significantly reduced by epinephrine (p < 0.0001). Body fat mass was associated with fasting leptin levels (r = 0.64, p < 0.0005) as well as with the decrease in leptinemia (r = −0.51, p < 0.01) produced by epinephrine administration. Furthermore, we noted a large range of leptin response to epinephrine among our subjects, especially in obese women (from −12 to −570 ng/mL per 60 minutes). However, there was no association between postepinephrine leptin and FFA levels (r = −0.14, p = 0.55). Discussion: Results of this study indicate that leptin levels decrease after epinephrine administration in both lean and obese premenopausal women. However, the heterogeneity in the response of leptin to catecholamines suggests potential alterations of the leptin axis that may contribute to generate a positive energy balance and, thus, may favor weight gain in some obese individuals.     

Leptin Levels,Leptin Receptor Gene Polymorphisms,and Energy Metabolism in Women

Objective: Resting metabolic rate (RMR) is mainly determined by fat‐free mass and additionally by age, sex, hormones, and possibly genetic differences. We evaluated whether leptin levels and polymorphisms in the leptin receptor (LEPR) gene were associated with energy expenditure phenotypes. Methods: RMR, body composition, and leptin levels were measured in 125 overweight and obese women. Three LEPR polymorphisms, Lys109Arg, Gln223Arg, and Lys656Asn, were typed on genomic DNA of another group of 192 women in whom RMR was measured. Fat, protein, and carbohydrate oxidation were calculated for 103 of these subjects. In 38 subjects, glucose‐induced thermogenesis was measured over 3 hours. Results: In the first study group, a negative correlation between RMR and leptin levels was found after controlling for fat and fat‐free mass. In multiple regression analysis, leptin contributed significantly to RMR, independent of body composition. In the second study group, RMR was not associated with LEPR polymorphisms. Differences in substrate oxidation rates were found among genotypes at the Lys656Asn site. In fasting conditions, Lys656Lys showed a trend to oxidize more carbohydrates and less fat than Asn656 carriers, a trend which became significant after the glucose load when carbohydrate oxidation rate in Lys656Lys was 15% higher than in Asn656 carriers (p = 0.04), and fat oxidation rate was 44% lower (p = 0.02). Discussion: These results suggest that DNA sequence variations in the LEPR gene could affect substrate oxidation. We hypothesize that this might be caused by differences in glucose levels, leading to differences in glucose oxidation rates.     

Impact of Visceral Fat on Blood Pressure and Insulin Sensitivity in Hypertensive Obese Women

Objective: The relationship among body fat distribution, blood pressure, serum leptin levels, and insulin resistance was investigated in hypertensive obese women with central distribution of fat. Research Methods and Procedures: We studied 74 hypertensive women (age, 49.8 ± 7.5 years; body mass index, 39.1 ± 5.5 kg/m²; waist-to-hip ratio, 0.96 ± 0.08). All patients were submitted to 24-hour blood pressure ambulatory monitoring (24h-ABPM). Abdominal ultrasonography was used to estimate the amount of visceral fat (VF). Fasting blood samples were obtained for serum leptin and insulin determinations. Insulin resistance was estimated by homeostasis model assessment insulin resistance index (HOMA-r index). Results: Sixty-four percent of the women were postmenopausal, and all patients showed central distribution of fat (waist-to-hip ratio > 0.85). The VF correlated with systolic 24h-ABPM values (r = 0.28, p = 0.01) and with HOMA-r index (r = 0.27; p = 0.01). VF measurement (7.5 ± 2.3 vs. 5.9 ± 2.2 cm, p < 0.001) and the systolic 24h-ABPM (133 ± 14.5 vs. 126 ± 9.8 mm Hg, p = 0.04), but not HOMA-r index, were significantly higher in the postmenopausal group (n = 48) than in the premenopausal group (n = 26). No correlations were observed between blood pressure levels and HOMA-r index, leptin, or insulin levels. In the multiple regression analysis, visceral fat, but not age, body fat mass, or HOMA-r index, correlated with the 24h-ABPM (p = 0.003). Discussion: In centrally obese hypertensive women, the accumulation of VF, more often after menopause, is associated with higher levels of blood pressure and insulin resistance. The mechanism through which VF contributes to higher blood pressure levels seems to be independent of leptin or insulin levels.     

Body composition of obese subjects by air displacement plethysmography: The influence of hydration

Objective: We investigated whether air displacement plethysmography (ADP) could detect small changes in body composition of obese subjects with alterations in hydration. Research Methods and Procedures: Ten obese subjects (mean BMI, 39.3 ± 2.8 kg/m²) entered the ADP chamber without and with oil (1, 2, or 4 liters), water (1, 2, or 4 liters), or mixed (1 liter oil + 1 liter water or 2 liters oil + 2 liters water) loads. Real and measured changes in body composition were compared by regression analysis and Bland‐Altman procedures. Results: The ADP‐measured changes in volume did not differ from the real values and were strongly correlated with them (r = 0.98). In all cases, loads of differing composition and similar volume led to different values of fat, fat‐free mass, and percentage fat. Water was detected as increased fat‐free mass only with loads of ≥2 liters, most of the water being falsely detected as increased fat mass. The observed changes were correlated with the real ones for fat mass (r = 0.68; p < 0.0001), fat‐free mass (r = 0.66; p < 0.0001), and percentage fat (r = 0.61; p < 0.0001), but fat mass changes were overestimated by ～1 kg, and fat‐free mass changes were underestimated by ～1 kg. This underestimation increased with the highest water loads, as shown by the Bland‐Altman plot (r = ?0.27; p < 0.05). Percentage fat changes were overestimated by 0.8% (p < 0.001); the magnitude of the error was correlated with the weight of the water load (r = 0.62; p < 0.0001). Discussion: ADP accurately measures changes in body volume, discriminating small changes in body composition. It overestimates changes in adiposity, as most of the increased hydration is detected as an enlarged fat mass.     

Resistin,Adiponectin, Ghrelin,Leptin, and Proinflammatory Cytokines: Relationships in Obesity

Objective: To evaluate interactions among leptin, adiponectin, resistin, ghrelin, and proinflammatory cytokines [tumor necrosis factor receptors (TNFRs), interleukin‐6 (IL‐6)] in nonmorbid and morbid obesity. Research Methods and Procedures: We measured these hormones by immunoenzyme or radiometric assays in 117 nonmorbid and 57 morbidly obese patients, and in a subgroup of 34 morbidly obese patients before and 6 months after gastric bypass surgery. Insulin resistance by homeostasis model assessment, lipid profile, and anthropometrical measurements were also performed in all patients. Results: Average plasma lipids in morbidly obese patients were elevated. IL‐6, leptin, adiponectin, and resistin were increased and ghrelin was decreased in morbidly obese compared with nonmorbidly obese subjects. After adjusting for age, gender, and BMI in nonmorbidly obese, adiponectin was positively associated with HDLc and gender and negatively with weight (β = ?0.38, p < 0.001). Leptin and resistin correlated positively with soluble tumor necrosis factor receptor (sTNFR) 1 (β = 0.24, p = 0.01 and β = 0.28, p = 0.007). In the morbidly obese patients, resistin and ghrelin were positively associated with sTNFR2 (β = 0.39, p = 0.008 and β = 0.39, p = 0.01). In the surgically treated morbidly obese group, body weight decreased significantly and was best predicted by resistin concentrations before surgery (β = 0.45, p = 0.024). Plasma lipids, insulin resistance, leptin, sTNFR1, and IL‐6 decreased and adiponectin and ghrelin increased significantly. Insulin resistance improved after weight loss and correlated with high adiponectin levels. Discussion: TNFα receptors were involved in the regulatory endocrine system of body adiposity independently of leptin and resistin axis in nonmorbidly obese patients. Our results suggest coordinated roles of adiponectin, resistin, and ghrelin in the modulation of the obesity proinflammatory environment and that resistin levels before surgery treatment are predictive of the extent of weight loss after bypass surgery.     

Total and Regional Fat and Serum Cardiovascular Disease Risk Factors in Lean and Obese Children and Adolescents

Objective: This study was conducted to evaluate the association of total and central adiposity with serum cardiovascular disease (CVD) risk factors in lean and obese Portuguese children and adolescents. Research Methods and Procedures: A total of 87 girls (13.2 ± 1.6 years old, 29.9 ± 6.4% body fat [mean ± SD]) and 72 boys (13.2 ± 1.6 years old, 20.8 ± 9.9% body fat) volunteered for the study. Whole‐body composition and fat distribution, from DXA and anthropometry, and serum lipids, lipoproteins, and apolipoproteins were evaluated. Results: The sum of three trunk skinfolds (STS) was highly correlated with total trunk fat mass measured by DXA (p < 0.001). Body mass index, DXA‐measured percentage of body fat, trunk fat mass, STS, and the waist‐to‐height ratio were generally found to be associated with triacylglycerol, the ratio of total cholesterol (TC) to high density lipoprotein‐cholesterol (HDL‐C), low density lipoprotein‐cholesterol (LDL‐C), and apolipoprotein B levels, (significant age‐adjusted r between 0.16 and 0.27, p < 0.05). Body mass index, STS, and the waist circumference were also associated with HDL‐C (p < 0.05), whereas no body composition variable significantly correlated with TC or apolipoproteins A‐I. The STS was significantly correlated with HDL‐C (p < 0.01), TC/HDL‐C (p < 0.05), and apolipoproteins A‐I (p < 0.05) independently of whole‐body fatness. Obese subjects (n = 73) had higher TC, LDL‐C, TC/HDL‐C, and apolipoprotein B than did non‐obese subjects (n = 86), and significant associations between central adiposity and some lipid variables (triacylglycerol and HDL‐C) were found in obese children and adolescents that were not present in leaner individuals. Discussion: DXA‐ and anthropometry‐based whole‐body and central fat measures are associated with serum CVD risk factors in Portuguese boys and girls. Obese children and adolescents have a poorer lipid profile than do their leaner counterparts. Trunk skinfolds, which are easy to obtain even in large samples, predict CVD risk factors to the same extent as DXA‐based variables, in some cases, independently of total fatness.