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Background/objectives: Increased adiposity, shorter stature, shorter leg length and carotid intima-media thickening are associated with cardiovascular (CV) disease. This study aimed to evaluate the sex-specific phenotypic and genetic associations between adiposity and anthropometric measures and carotid intima-media thickness (IMT)., Subjects/methods: We measured IMT at common carotid artery (CCA-IMT), carotid bifurcation and internal carotid artery (ICA-IMT) using B-mode ultrasound, and adiposity and anthropometric measures, including body mass index (BMI), height, leg length, waist circumference (WC), waist-to-hip ratio and percentage of body fat; we also assessed conventional CV risk factors among 706 Korean adults from the Healthy Twin Study. The associations were analyzed using quantitative genetic and linear mixed analyses., Results: In linear mixed analyses, BMI and WC had independent associations with the IMT at CCA-IMT and ICA-IMT and CCA-IMT, respectively, after adjusting for age and conventional CV risk factors in men. By comparison, in women, adiposity and anthropometric measures were associated with carotid IMT only before adjusting for the covariates. In men, there were significant genetic correlations between BMI and CCA-IMT (ρ(G)=0.32±0.11), BMI and ICA-IMT (ρ(G)=0.35±0.11) and WC and ICA-IMT (ρ(G)=0.32±0.13) after adjusting for covariates, whereas in women the cross-trait genetic correlations were no longer significant after adjusting for the covariates., Conclusions: In this Korean twins and families, we found sex-specific associations between adiposity and anthropometric measures and the IMT at each segment of the carotid artery, and BMI and WC in men can be indicators predicting carotid intima-media thickening regardless of age and CV risk factors.

Obese individuals have hyperleptinemia and hypozincemia. Moreover, leptin and zinc have circadian changes in circulating concentrations. We investigated their possible interaction and examined whether a difference existed between obese men and their lean controls. The results indicated the pattern of circadian change in plasma zinc and leptin did not markedly differ between the obese subjects and the lean controls. However, the obese had higher leptin and lower zinc plasma values at each sampling time than did the lean controls. Because an inverse correlation was found in plasma values between zinc and leptin (r=-0.51, p=0.012), we further determined the role zinc might play in leptin production by human subcutaneous adipose tissue from female donors. The in vitro study showed that zinc treatment (0.2 mmol/L) significantly increased leptin production (142%), however, this increment did not surpass that by insulin (10 nmol/L). The data of this study suggest an interactive connection between zinc and leptin.

Background: beta 3-Adrenergic receptors are predominantly expressed in the fat cells of visceral adipose tissue in humans. They mediate catecholamine-induced lipolysis and thermogenesis of adipose tissue, which are important for the regulation of energy expenditure and, therefore, body weight. Recently, a Trp64Arg polymorphism of the beta 3-adrenergic receptor gene was reported to be associated with obesity and obesity-related metabolic complications in some ethnic populations. Leptin, a protein secreted by adipocytes, is proposed as a signal linkage between the central nervous system and peripheral fat storage. It has been shown in rodents that leptin may activate the sympathetic nervous system and, thus, beta 3-adrenergic receptors in adipose tissue. However, little is known about the relationship between the Trp64Arg polymorphism and plasma leptin in humans., Methods: To determine the effects of the beta 3-adrenergic receptor gene Trp64Arg mutation on anthropometric measures, metabolic parameters and plasma leptin levels, 188 premenopausal Chinese women (mean age +/- standard deviation, 32 +/- 10 years) with body mass index (BMI) between 16.1 and 59.8 kg/m2 were investigated. Trp64Arg polymorphism was determined by DNA analysis, body fat mass by bioelectric impedance analysis and plasma leptin by radioimmunoassay., Results: Trp64Arg allele frequency was 15% in this population and there was no homozygous Arg64Arg mutant. When the subjects were divided into three groups based on BMI values (BMI < 22.2, n = 60; 22.2 < or = BMI < or = 29.5, n = 63; BMI > 29.5 kg/m2, n = 65), there was no difference in Trp64Arg allele frequency (16% vs 11% vs 18%, p = 0.149). Across the three groups, plasma leptin correlated positively with BMI (r = 0.843, p < 0.0001) and total fat mass (r = 0.824, p < 0.0001). Within each BMI tertile, the waist to hip ratio, fat mass, plasma lipids, glucose and insulin were relatively similar between Trp64Trp homozygotes and Trp64Arg heterozygotes. However, Trp64Arg heterozygotes had higher plasma leptin levels than Trp64Trp homozygotes (35.9 +/- 11.0 vs 30.0 +/- 12.8 ng/ml, p = 0.0023) in those with BMI above 29.5 kg/m2, a difference which remained after adjustment for body fat mass (p = 0.024)., Conclusions: Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not associated with obesity in Chinese women. Plasma leptin concentrations correlate well with BMI and total fat mass. For obese Chinese women, the Trp64Arg genotype of the beta 3-adrenergic receptor gene may contribute to an increased plasma leptin level.

Background: Most obesities are known low in sympathetic activity, and brain neurotransmitters may play roles in the defective exhibitions of obesity. Caffeine, a stimulant, which can prompt lipolysis, has been applied on the therapy of obesity. Although the interactive combinations between caffeine and certain neurotransmitters has been appreciated recently, but its regulatory mechanisms are still obscure. This study investigated the effect of caffeine on the body fat deposition, and its interactions with brain serotonin and catecholamine in the genetically obese (ob/ob) mice., Methods: At 12-week of age, obese mice and their lean counterparts (+/?) were administered with caffeine (4 mg/d) in water for 4 weeks. The brain neurotransmitters levels and body fat content were measured., Results: The obese mice without caffeine treatment had lower brain norepinephrine and epinephrine levels than the lean controls. And there had no difference between obese and lean mice in brain levels of serotonin, tryptophan, and 5-hydroxyindoleacetic acid. Caffeine treatment showed no effect on the food intake, but decreased the body fat content significantly in obese mice. Mice with caffeine treatment showed increase of the levels of brain neurotransmitters in both phenotypes; this effect was more predominant in obese mice., Conclusions: This study indicated that the effect of caffeine to decrease body fat deposition in the obese mice might be associated with the recovered increases of sympathetic activity.

To determine whether improved metabolic control with long term glyburide treatment alters intracellular glucose metabolism independent of effects on glucose uptake (GU), we studied eight obese patients with noninsulin-dependent diabetes mellitus before and 7 months after glyburide therapy. Indirect calorimetry and skeletal muscle biopsies were performed in the basal state and during 300 pmol/m2.min insulin infusions, with glucose turnover rates determined by [3-3H]glucose turnover. During the glucose clamps, rates of GU were matched before and after treatment using equivalent hyperinsulinemia and variable levels of hyperglycemia. After glyburide treatment, rates of GU were decreased in the basal state [4.16 +/- 0.57 vs. 3.29 +/- 0.37 mg/kg fat free mass (FFM)/min; P < 0.05], but similar during glucose clamps (11.53 +/- 1.42 vs. 11.93 +/- 1.32 mg/kg FFM.min; P = NS) according to study design. In both the basal state and during glucose clamps after glyburide therapy, rates of glucose oxidative metabolism (Gox) increased by 68-78% [1.21 +/- 0.16 vs. 2.03 +/- 0.31 mg/kg FFM.min (P < 0.05) and 3.13 +/- 0.51 vs. 5.58 +/- 0.55 mg/kg FFM.min (P < 0.05), respectively], and rates of nonoxidative glucose metabolism decreased [2.96 +/- 0.68 vs. 1.25 +/- 0.21 mg/kg FFM.min (P < 0.05) and 8.40 +/- 1.50 to 6.30 +/- 1.40 mg/kg FFM.min (P < 0.01), respectively]. Circulating plasma FFA levels and rates of fat oxidation (Fox) remained unchanged in both the basal state and during clamp studies. Skeletal muscle glycogen synthase (GS) activity, expressed as fractional velocity, was unchanged by glyburide therapy (2.2 +/- 0.8 vs. 2.7 +/- 0.3% in the basal state and 7.3 +/- 1.8 vs. 6.1 +/- 0.9% during clamps; both P = NS). In summary, at both matched (during clamp studies) and unmatched (during basal studies) rates of GU, improved metabolic control with glyburide therapy resulted in marked improvement of Gox independent of the effects on GU. The improvement in Gox was not associated with changes in Fox, circulating FFA, or muscle GS activity. These data indicate that long term metabolic control achieved by glyburide therapy markedly improves Gox, but not skeletal muscle GS activity, in noninsulin-dependent diabetes mellitus independent of GU and Fox.