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.     

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.     

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 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.     

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.     

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 Weight Loss and Weight Maintenance in Relation to Habitual Caffeine Intake and Green Tea Supplementation

Objective: Investigation of the effect of a green tea‐caffeine mixture on weight maintenance after body weight loss in moderately obese subjects in relation to habitual caffeine intake. Research Methods and Procedures: A randomized placebo‐controlled double blind parallel trial in 76 overweight and moderately obese subjects, (BMI, 27.5 ± 2.7 kg/m²) matched for sex, age, BMI, height, body mass, and habitual caffeine intake was conducted. A very low energy diet intervention during 4 weeks was followed by 3 months of weight maintenance (WM); during the WM period, the subjects received a green tea‐caffeine mixture (270 mg epigallocatechin gallate + 150 mg caffeine per day) or placebo. Results: Subjects lost 5.9 ±1.8 (SD) kg (7.0 ± 2.1%) of body weight (p < 0.001). At baseline, satiety was positively, and in women, leptin was inversely, related to subjects’ habitual caffeine consumption (p < 0.01). High caffeine consumers reduced weight, fat mass, and waist circumference more than low caffeine consumers; resting energy expenditure was reduced less and respiratory quotient was reduced more during weight loss (p < 0.01). In the low caffeine consumers, during WM, green tea still reduced body weight, waist, respiratory quotient and body fat, whereas resting energy expenditure was increased compared with a restoration of these variables with placebo (p < 0.01). In the high caffeine consumers, no effects of the green tea‐caffeine mixture were observed during WM. Discussion: High caffeine intake was associated with weight loss through thermogenesis and fat oxidation and with suppressed leptin in women. In habitual low caffeine consumers, the green tea‐caffeine mixture improved WM, partly through thermogenesis and fat oxidation.     

The Effects of Metformin and Diet on Plasma Testosterone and Leptin Levels in Obese Men

Objective: The aim of this study was to investigate the effects of combined hypocaloric diet and metformin on circulating testosterone and leptin levels in obese men with or without type 2 diabetes. Research Methods and Procedures: Twenty obese men with type 2 diabetes (mean body mass index [BMI]: 35.5 ± 1.1 kg/m²) and 20 nondiabetic obese men were enrolled in the study. We measured serum follicle‐stimulating hormone, luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), sex‐hormone‐binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and plasma leptin levels before and 3 months after metformin treatment. Both groups were placed on a hypocaloric diet and 850 mg of metformin taken orally twice daily for 3 months. Results: Metformin and hypocaloric diets led to decreases in BMI and waist and hip circumferences in both groups. A significant decrease in TT levels in the diabetic group and FT levels in the control group was found, whereas follicle‐stimulating hormone, LH, and DHEAS levels were not changed significantly. A significant increase in SHBG levels was observed in the control group but not in the patient group. Leptin levels also decreased after treatment in both groups. Decreased testosterone levels were not correlated to changes in waist and hip circumference, waist‐to‐hip ratio, BMI, and levels of fasting blood glucose, leptin, SHBG, or DHEAS in the diabetic group. However, a decrease in FT was correlated to changes in the levels of SHBG (r = ?0.71, p = 0.001) and LH (r = 0.80, p = 0.001) but not to other parameters. Discussion: We conclude that metformin treatment combined with a hypocaloric diet leads to reduced FT levels in obese nondiabetic men and to reduced TT levels in obese men with type 2 diabetes. Increased SHBG levels may account for the decrease in FT levels in the former group.     

High Serum Leptin Is Associated with Attenuated Coronary Vasoreactivity

Objective: Hyperleptinemia, a hallmark of obesity, appears to be a risk factor for coronary artery disease. However, although leptin is a vasoactive hormone, no studies addressing leptin's effect on coronary perfusion have been performed. We examined the association between circulating leptin concentration and coronary vasoreactivity in young obese and nonobese males. Research Methods and Procedures: Myocardial blood flow was quantitated in 10 obese men (age 31 ± 7 years, BMI 34 ± 2 kg/m²) and 10 healthy matched nonobese men (age 33 ± 8 years, BMI 24 ± 2 kg/m²) using positron emission tomography and O‐15‐water. The measurements were performed basally and during adenosine infusion (140 μg/kg per minute). Results: Serum leptin was significantly higher in obese than nonobese subjects (10.3 ± 5.6 vs. 4.3 ± 2.5 ng/mL, p < 0.01). Basal myocardial blood flow was not significantly different between obese and nonobese subjects. Adenosine‐stimulated flow was blunted in obese (3.2 ± 0.6 mL/g per minute) when compared with nonobese subjects (4.0 ± 1.1 mL/g per minute, p < 0.05). Serum leptin concentration was inversely associated with adenosine‐stimulated flow in study subjects (r = ?0.50, p < 0.05). This association was no longer observed after adjustment for obesity and/or hyperinsulinemia. Discussion: Hyperleptinemia and reduced coronary vasoreactivity occur concomitantly in young obese but otherwise healthy men. Moreover, the adenosine‐stimulated myocardial flow is inversely related to prevailing concentration of serum leptin. Although this relationship appears to be explained by obesity and/or hyperinsulinemia, leptin might have a role in regulation of myocardial blood supply.     

Autonomic Nervous System Activity and the State and Development of Obesity in Japanese School Children

Objective: The autonomic nervous system (ANS) plays an important role in regulating energy expenditure and body fat content; however, the extent to which the ANS contributes to pediatric obesity remains inconclusive. The aim of this study was to evaluate whether sympathetic and/or the parasympathetic nerve activities were altered in an obese pediatric population. We further examined a physiological association between the duration of obesity and the sympatho‐vagal activities to scrutinize the nature of ANS alteration as a possible etiologic factor of childhood obesity. Research Methods and Procedures: Forty‐two obese and 42 non‐obese healthy sedentary school children were carefully selected from 1080 participants initially recruited to this study. The two groups were matched in age, gender, and height. The clinical records of physical characteristics and development of the obese children were retrospectively reviewed to investigate the onset and progression of obesity. The ANS activities were assessed during a resting condition by means of heart rate variability power spectral analysis, which enables us to identify separate frequency components, i.e., total power (TP), low‐frequency (LF) power, and high‐frequency (HF) power. The spectral powers were then logarithmically transformed for statistical testing. Results: The obese children demonstrated a significantly lower TP (6.77 ± 0.12 vs. 7.11 ± 0.04 ln ms², p < 0.05), LF power (6.16 ± 0.12 vs. 6.42 ± 0.05 ln ms², p < 0.05), and HF power (5.84 ± 0.15 vs. 6.34 ± 0.07 ln ms², p < 0.01) compared with the non‐obese children. A partial correlation analysis revealed that the LF and HF powers among 42 obese children were negatively associated with the duration of obesity independent of age (LF: partial r = ?0.55, p < 0.001; HF: partial r = ?0.40, p < 0.01). The obese children were further subdivided into two groups based on the length of their obesity. All three spectral powers were significantly reduced in the obese group with obesity of >3 years (n = 18) compared to the group with obesity of <3 years. Discussion: Our data indicate that obese children possess reduced sympathetic as well as parasympathetic nerve activities. Such autonomic depression, which is associated with the duration of obesity, could be a physiological factor promoting the state and development of obesity. These findings further imply that preventing and treating obesity beginning in the childhood years could be an urgent and crucial pediatric public health issue.     

Endothelial function and weight loss: Comparison of low‐carbohydrate and low‐fat diets

Objective: The effect of weight loss on obesity‐associated endothelial dysfunction is not clear because of conflicting data, demonstrating both improvement and no change in endothelial function after weight loss in obese subjects. A 2‐year prospective study (n = 121) was conducted to examine: (1) the effect of obesity and weight loss (either a low‐carbohydrate or and low‐fat diet) on flow mediated vasodilatation (FMD), a measure of endothelial function. Design and Methods: Participants reduced body weight by 7.1% ± 4.4%, 8.7% ± 6.8%, 7.1% ± 7.8%, and 4.1% ± 7.7% at 3, 6, 12, and 24 months, respectively with no significant differences between the low‐fat and low‐carbohydrate groups. Results: Endothelial function was inversely correlated with waist circumference, triglyceride level, and directly correlated with leptin in obese persons prior to weight loss. These weight losses did not confer any improvements in FMD. There were no differences between the low‐fat and low‐carbohydrate diets in FMD at any time point. At 6 months (r = 0.26, P = 0.04) and 1 year (r =0.28, P = 0.03), there were positive correlations between change in FMD and change in leptin but not at 2 years. Conclusion: There was no significant improvement in endothelial function after 7.1% ± 7.8% weight loss at 1 year and 4.1% ± 7.7% at 2 years, achieved by either a low carbohydrate or a low fat diet.     

Effect of Lifestyle Modification on Adipokine Levels in Obese Subjects with Insulin Resistance

Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty‐four insulin‐resistant obese subjects with varying degrees of glucose tolerance completed a 6‐month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)] and highly sensitive C‐reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 ± 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 ± 3 vs. 23.6 ± 3 ng/mL, p = 0.01) and IL‐6 (2.75 ± 1.51 vs. 2.3 ± 0.91 pg/mL, p = 0.012). TNF‐α levels tended to decrease (2.3 ± 0.2 vs. 1.9 ± 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C‐reactive protein (r = 0.466, p < 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL‐6 and a tendency toward a decrease in circulating TNF‐α, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.     

Gender Differences in the Response of Plasma Leptin Concentrations to Weight Loss in Obese Older Individuals

Plasma leptin concentration is directly related to the degree of obesity and is higher in women than in men of the same body mass index (BMI). We hypothesized that fasting plasma leptin concentrations and the response of leptin to weight loss would differ in older men and women of a similar fat mass. Plasma leptin concentrations (radioimmunoassay) and fat mass (DXA) were measured in 47 older, obese (BMI=30 ± 4 kg/m²) women and 23 older, obese (BMI=31 ± 3 kg/m²) men after a 2 to 4 week period of weight and dietary stabilization, and then in 22 of the women and 18 of the men after a 6-month weight loss intervention (250–350 kcal/d deficit). Leptin correlated with fat mass in men and women (r=0.75 and r=0.77, respectively; p values<0.0001), but women had 3-fold higher leptin levels for a given fat mass than men (p=0.01). In response to the 6-month hypocaloric diet, men and women lost a similar percentage of fat mass (?13% and ?16%, respectively), but the relative decline in circulating leptin was greater in women than men (-45% and ?21%, respectively; p<0.0001). In addition, when leptin was normalized for fat mass using the ratio method, the decrease in leptin per kilogram of fat mass was greater in women than men (-0.37 ± 0.34 vs. ?0.04 ± 0.06 ng/mL/kg; p<0.01). After weight loss, the change in leptin concentrations correlated positively with the change in fat mass in men (r=0.60; p<0.01), but not in women (r=0.31; p=0.17). Furthermore, the loss in fat mass correlated negatively with baseline leptin levels in women (r=-0.47; p<0.05), but not in men (r=0.03, p=NS). These results indicate that the decline in leptin concentration with weight loss correlates with the loss in fat mass in men; but, in women, other factors affect the decrease in leptin concentration. This suggests that the role of leptin in the regulation of obesity is gender-specific and may account for gender differences in response to hypocaloric treatment and maintenance of lost weight.     

Predictors of Long‐term Weight Maintenance

Objective: The purpose of this study was to evaluate available variables of a long‐term weight maintenance study to investigate possible factors predisposing to weight regain after a period of weight loss. Research Methods and Procedures: The Maastricht Weight Maintenance Study is an ongoing longitudinal study of healthy men and women (29 men and 62 women; 18 to 65 years of age; BMI = 30.2 ± 3.1 kg/m²). A variety of parameters were measured before and after a very‐low‐energy diet and after a follow‐up of at least 2 years. Results: Mean weight loss was 7.9 ± 3.6 kg, and percent weight regain was 113.8 ± 98.1%. Percent BMI regain was negatively associated with an increase in dietary restraint (r = ?0.47, p < 0.05). Percent weight regain was negatively correlated with baseline resting metabolic rate (r = ?0.38, p = 0.01) and baseline fat mass (r = ?0.24, p = 0.05) and positively correlated with the magnitude of change in body weight (BW) expressed as maximum amplitude of BW (r = 0.21, p < 0.05). In addition, amplitude of BW was positively correlated with the frequency of dieting (r = 0.57, p < 0.01). Discussion: The best predictors for weight maintenance after weight loss were an increase in dietary restraint during weight loss, a high baseline resting metabolic rate, a relatively high baseline fat mass favoring a fat‐free mass–sparing effect during weight loss, a rather stable BW, and a low frequency of dieting. Therefore, BW maintenance after BW loss seems to be a multifactorial issue, including mechanisms that regulate an individuals’ energy expenditure, body composition, and eating behavior in such a way that energy homeostasis is maintained.     

Weight Loss Increases Soluble Leptin Receptor Levels and the Soluble Receptor Bound Fraction of Leptin

Objective: Soluble leptin receptor (sOB‐R) represents the main binding site for leptin in human blood. The aim of this study was to investigate the relationship between leptin and soluble leptin receptor and the bound/free ratio after pronounced weight reduction. Research Methods and Procedures: A total of 18 morbidly obese women participated in this prospective study. Subjects were examined for fat mass, leptin, and sOB‐R concentrations before and 1 year after Swedish adjustable gastric banding. Results: Anthropomorphic measures displayed a significant reduction of body mass index [(42.9 ± 5.6 to 32.9 ± 6.0 kg/m² (mean ± SD)]. Fat mass decreased from 56.3 ± 9.0 to 33.9 ± 12.5 kg. Plasma leptin concentration decreased from 44.6 ± 18.0 to 20.0 ± 13.1 ng/mL (p < 0.001), whereas the sOB‐R levels increased from 11.1 ± 3.6 to 16.6 ± 6.0 U/mL after weight‐reducing surgery. Thus, the sOB‐R bound fraction of leptin increased from 7% to 33%. Discussion: This work demonstrates a relationship between weight loss, leptin, and sOB‐R concentrations in vivo. During weight loss, leptin levels decreased, whereas sOB‐R levels and the receptor bound fraction of leptin increased. Thus, sOB‐R may negatively regulate free leptin.     

Racial Differences in Metabolic Predictors of Obesity among Postmenopausal Women

NICKLAS, BARBARA S., DORA M. BERMAN, DAWN C. DAVIS, C. LYNNE DOBROVOLNY, AND KAREN E. DENNIS. Racial differences in metabolic predictors of obesity among postmenopausal women. Ober Res. Objective: This study determined whether there are racial differences in resting metabolic rate (RMR), fat oxidation, and maximal oxygen consumption (VO,max) in obese [body mass index (BMI = 34±2 kg/m²)], postmenopausal (58±2 years) women. Research Methods and Procedures: Twenty black and 20 white women were matched for fat mass and lean mass (LM), as determined by dual energy X-ray absorptiometry. RMR and fat oxidation were measured by indirect calorimetry in the early morning after a 12-hour fast using the ventilated hood technique. VO₂max was measured on a treadmill during a progressive exercise test to voluntary exhaustion. Results: RMR, adjusted for differences in LM, was 5% higher in white than black women (1566±27 and 1490±26 kcal/day, respectively; p<0. 05); and fat oxidation rate was 17% higher in white than black women (87±4 and 72±3 g/day, respectively; p<0. 01). VO₂max (L/minute) was 150 mL per minute (8%) higher (p<0. 05) in white than black women. VO₂max correlated with LM in black (r = 0. 44, p = 0. 05) and white (r=0. 53, p<0. 05) women, but the intercept of the regression line was higher in white than black women (p<0. 05), with no significant difference in slopes. In a multiple regression model including race, body weight, LM, and age, LM was the only independent predictor of RMR (r² = 0. 46, p<0. 0001), whereas race was the only independent predictor of fat oxidation (r² = 0. 18,p<0. 05). The best predictors of VO,max were LM (r² = 0. 22, p<0. 05) and race (cumulative r² = 0. 30, p<0. 05). Discussion: These results show there are racial differences in metabolic predictors of obesity. Determination of whether these ethnic differences lead to, or are an effect of, obesity status or other lifestyle factors requires further study.     

Enhanced Erythrocyte Adhesiveness/Aggregation in Obesity Corresponds to Low‐Grade Inflammation

Objective: Previous studies have suggested that obesity enhances the inflammatory response, producing macromolecules involved in the induction and/or maintenance of increased erythrocyte aggregation. The objectives of this study were to evaluate the correlation between inflammation markers, erythrocyte adhesiveness/aggregation, and the degree of obesity and to assess phosphatidylserine expression on erythrocyte surface membrane of obese vs. nonobese individuals. Research Methods and Procedures: Erythrocyte adhesiveness/aggregation in the peripheral venous blood was evaluated by using a new biomarker, phosphatidylserine expression was assessed by means of flow cytometry, and markers of inflammation were measured in 65 subjects: 30 obese [body mass index (BMI) = 41 ± 7.7 kg/m²] and 35 nonobese (BMI = 24 ± 2.7 kg/m²) individuals. Pearson correlations and Student's t test were performed. Results: A highly significant difference was noted in the degree of erythrocyte adhesiveness/aggregation and markers of inflammation between the study groups. BMI correlated with erythrocyte adhesiveness/aggregation (r = 0.42, p = 0.001), erythrocyte sedimentation rate (r = 0.42, p = 0.001), high‐sensitive C‐reactive protein (r = 0.55, p < 10^?4), fibrinogen (r = 0.37, p = 0.004), and white blood cell count (r = 0.45, p < 10^?4). The degree of erythrocyte adhesiveness/aggregation correlated with erythrocyte sedimentation rate (r = 0.5, p < 10^?4), high‐sensitive C‐reactive protein (r = 0.56, p < 10^?4), fibrinogen (r = 0.54, p < 10^?4), and white blood cell count (r = 0.32, p = 0.01). Discussion: Our results suggest that obesity‐related erythrocyte adhesiveness/aggregation is probably mediated through increased concentrations of adhesive macromolecules in the circulation and not necessarily through hyperlipidemia or phosphatidylserine exposure on erythrocyte's membrane.     

Methods of Estimation of Visceral Fat: Advantages of Ultrasonography

Objective: To compare methods for the assessment of visceral fat with computed tomography (CT) and establish cutoffs to define visceral obesity based on such alternative methods. Research Methods and Procedures: One hundred women (50.4 ± 7.7 years; BMI 39.2 ± 5.4 kg/m²) underwent anthropometric evaluation, bioelectrical impedance, DXA, abdominal ultrasonography (US), and CT scan. Results: Waist circumference, waist‐to‐hip ratio (WHR), and US‐determined visceral fat values showed the best correlation coefficients with visceral fat determined by CT (r = 0.55, 0.54, and 0.71, respectively; p < 0.01). Fat mass determined by DXA was inversely correlated with visceral‐to‐subcutaneous‐fat ratio (r = ?0.47, p < 0.01). Bioimpedance‐determined fat mass and skinfolds were correlated with only subcutaneous abdominal fat quantified by CT. Linear regression indicated US visceral‐fat distance and WHR as the main predictors of CT‐determined visceral fat (adjusted r² = 0.51, p < 0.01). A waist measurement of 107 cm (82.7% specificity, 60.6% sensitivity) and WHR of 0.97 (78.8% specificity, 63.8% sensitivity) were chosen as discriminator values corresponding with visceral obesity diagnosed by CT. A value of 6.90 cm for visceral fat US‐determined diagnosed visceral obesity with a specificity of 82.8%, a sensitivity of 69.2%, and a diagnostic concordance of 74% with CT. Discussion: US seemed to be the best alternative method for the assessment of intra‐abdominal fat in obese women. Its diagnostic value could be optimized by an anthropometric measurement. Prospective studies are needed to establish CT and US cutoffs for defining visceral‐fat levels related to elevated cardiovascular risk.     

Leptin, superoxide dismutase, and weight loss: initial leptin predicts weight loss

Objective: Our goal was to study how plasma leptin concentration, superoxide dismutase (SOD) activity, and weight loss are related in obese adults. Research Methods and Procedures: Serum leptin concentration, SOD activities, general biochemical data, and body composition measurements were obtained for 62 overweight and obese subjects before and after an 8‐week body weight reduction (BWR) regimen. The subjects were on dietary control, performed moderate aerobic and strength training exercises, and attended educational lectures. Results: The measurement results indicated that the following criteria were significantly reduced: body weight [84.4 ± 17.0 vs. 79.3 ± 16.1 (standard error) kg, p < 0.001]; BMI (31.5 ± 4.3 vs. 29.4 ± 4.2 kg/m², p < 0.001), and fat mass (33.3 ± 10.0 vs. 29.8 ± 10.4 kg, p < 0.001). Plasma leptin levels also significantly decreased from 31.5 ± 17.6 to 26.5 ± 17.2 ng/mL (p < 0.001). Additionally, SOD activity was significantly increased from 261.4 ± 66.0 to 302.7 ± 30.9 U/mL (p < 0.001). Based on linear regression analysis results, a 3.78‐ to 8.13‐kg reduction in weight can be expected after the 8‐week BWR regimen when initial leptin concentration was 5 to 30 ng/mL. Discussion: We found that an 8‐week exercise and diet program was effective in reducing weight and fat mass and, notably, had further beneficial effects on leptin resistance and SOD activity. Additionally, this study demonstrated that initial plasma leptin concentration may be used as a predictor for weight loss outcome.     

Weight Loss Reduces Tissue Factor in Morbidly Obese Patients

Objective: To investigate the tissue factor (TF) pathway in clinical obesity and associated metabolic syndrome. Research Methods and Procedures: Thirty‐seven morbidly obese patients (4 men; BMI, 48 ± 7 kg/m²; range, 42 to 53 kg/m²), undergoing elective gastroplasty for the induction of weight loss, were examined for hemostatic, metabolic, and inflammatory parameters at baseline and 14 ± 5 months postoperatively. Results: Weight loss significantly reduced circulating plasma TF (314 ± 181 vs. 235 ± 113 pg/mL, p = 0.04), coagulation factor VII (130 ± 22% vs. 113 ± 19%, p = 0.023), and prothrombin fragment F1.2 (2.4 ± 3.4 vs. 1.14 ± 1.1 nM, p = 0.04) and normalized glucose metabolism in 50% of obese patients preoperatively classified as diabetic or of impaired glucose tolerance. The postoperative decrease in plasma TF correlated with the decrease of F1.2 (r = 0.56; p = 0.005), a marker of in vivo thrombin formation. In subgroup analysis stratified by preoperative glucose tolerance, baseline circulating TF (402.6 ± 141.6 vs. 176.2 ± 58.2, p < 0.001) and TF decrease after gastroplasty (ΔTF: 164.7 ± 51.4 vs. ?81 ± 31 pg/mL, p = 0.02) were significantly higher in obese patients with impaired glucose tolerance than in patients with normal glucose tolerance. Discussion: Procoagulant TF is significantly reduced with weight loss and may contribute to a reduction in cardiovascular risk associated with obesity.