Visceral and subcutaneous adipose tissue display important metabolic differences that underlie the association of visceral obesity with obesity-related cardiovascular and metabolic alterations. Recently, visfatin was identified as an adipokine, which is predominantly secreted from visceral adipose tissue both in humans and mice. In this study, we examined whether visfatin plasma concentrations (using enzyme immunosorbent assay) and mRNA expression (using RT-PCR) in visceral and subcutaneous fat correlates with anthropometric and metabolic parameters in 189 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance. Visfatin plasma concentration correlates positively with the visceral visfatin mRNA expression (r 2 ‫؍‬ 0.17, P < 0.0001), BMI (r 2 ‫؍‬ 0.062, P ‫؍‬ 0.004), percent body fat (r 2 ‫؍‬ 0.048, P ‫؍‬ 0.01), and negatively with subcutaneous visfatin mRNA expression (r 2 ‫؍‬ 0.18, P < 0.0001). However, in a subgroup of 73 individuals, in which visceral fat mass was calculated from computed tomography scans, there was no correlation between plasma visfatin concentrations and visceral fat mass. We found no significant correlation between visfatin plasma concentrations and parameters of insulin sensitivity, including fasting insulin, fasting plasma glucose concentrations, and the glucose infusion rate during the steady state of an euglycemic-hyperinsulinemic clamp independent of percent body fat. Visfatin gene expression was not different between visceral and subcutaneous adipose tissue in the entire study group nor in selected subgroups. We found a significant correlation between visceral visfatin gene expression and BMI (r 2 ‫؍‬ 0.06, P ‫؍‬ 0.001) and percent body fat (measured using dual-energy X-ray absorptiometry) (r 2 ‫؍‬ 0.044, P ‫؍‬ 0.004), whereas no significant association between BMI or percent body fat and subcutaneous visfatin mRNA expression existed (both P >0.5). In conclusion, visfatin plasma concentrations and visceral visfatin mRNA expression correlated with measures of obesity but not with visceral fat mass or waist-tohip ratio. In addition, we did not find differences in visfatin mRNA expression between visceral and subcutaneous adipose tissue in humans. Diabetes 54:2911-2916, 2005 E pidemiological and animal studies reported an association between increased visceral obesity and the prevalence of insulin resistance, type 2 diabetes, and the risk of cardiovascular disease (rev. in 1-3). Moreover, differences in gene expression of adipocyte-secreted molecules suggest that there are intrinsic fat depot-specific differences in the endocrine function of adipose tissue. These differentially expressed adipokines include leptin (4,5), plasminogen activator inhibitor-1 (6), and interleukin-6 (7).Recently, visfatin was identified as a peptide predominantly expressed in and secreted from visceral adipose tissue in both humans and mice (8). This peptide was previously described as a growth factor for early B-cells called pre-B-cell colony-enhancing factor (...

Obesity, especially central obesity, is a hereditable trait associated with a high risk for development of diabetes and metabolic disorders. Combined gene expression analysis of adipocyte-and preadipocyte-containing fractions from intraabdominal and subcutaneous adipose tissue of mice revealed coordinated depotspecific differences in expression of multiple genes involved in embryonic development and pattern specification. These differences were intrinsic and persisted during in vitro culture and differentiation. Similar depot-specific differences in expression of developmental genes were observed in human subcutaneous versus visceral adipose tissue. Furthermore, in humans, several genes exhibited changes in expression that correlated closely with body mass index and͞or waist͞hip ratio. Together, these data suggest that genetically programmed developmental differences in adipocytes and their precursors in different regions of the body play an important role in obesity, body fat distribution, and potential functional differences between internal and subcutaneous adipose tissue.adipose tissue ͉ gene expression ͉ subcutaneous ͉ intraabdominal

Intra-abdominal fat is associated with insulin resistance and cardiovascular risk. Levels of serum retinol-binding protein (RBP4), secreted by fat and liver cells, are increased in obesity and type 2 diabetes (T2D). Here we report that, in 196 subjects, RBP4 is preferentially expressed in visceral (Vis) versus subcutaneous (SC) fat. Vis fat RBP4 mRNA was increased approximately 60-fold and 12-fold in Vis and SC obese subjects respectively versus lean subjects, and approximately 2-fold with impaired glucose tolerance/T2D subjects versus normoglycemic subjects. In obese subjects, serum RBP4 was increased 2- to 3-fold, and serum transthyretin, which stabilizes RBP4 in the circulation, was increased 35%. Serum RBP4 correlated positively with adipose RBP4 mRNA and intra-abdominal fat mass and inversely with insulin sensitivity, independently of age, gender, and body mass index. RBP4 mRNA correlated inversely with GLUT4 mRNA in Vis fat and positively with adipocyte size in both depots. RBP4 levels are therefore linked to Vis adiposity, and Vis fat may be a major source of RBP4 in insulin-resistant states.

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