DIFFERENTIAL REGULATION OF THE P80 TUMOR-NECROSIS-FACTOR RECEPTOR IN HUMAN OBESITY AND INSULIN-RESISTANCE

Previous studies have shown that tumor necrosis factor (TNF)-alpha pro duction from adipose tissue is elevated in rodent and human obesity an d plays an important role in insulin resistance in experimental animal models. In this study, we examined the adipose expression of both TNF receptors (TNFR1 and TNFR2) in human obesity and demonstrated that ob ese female subjects express approximately twofold more TNFR2 mRNA in f at tissue and approximately sixfold more soluble TNFR2 in circulation relative to lean control subjects. In contrast, TNFR1 expression and p rotein levels were similar in these subjects, TNFR2 expression levels in adipose tissue were strongly correlated with BMI (r = 0.65, P < 0.0 01) and level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance, as well as level of TNF-alpha mRNA expression in f at tissue (r = 0.56, P < 0.001). These results suggest that TNFR2 migh t play a role in human obesity by modulating the actions of TNF-alpha.