Effect of troglitazone on tumor necrosis factor α and transforming growth factor β expression and action in human adipocyte precursor cells in primary culture

Troglitazone is a member of the class of thiazolidinediones that are known to act as insulin-sensitizing agents. Administration of these compounds ameliorates insulin resistance in type 2 diabetic patients, but may also promote weight gain. The main site of action is adipose tissue, where troglitazone binds to and activates the nuclear receptor peroxisome proliferator–activated receptor γ2. The aim of this study was to investigate whether troglitazone is able to affect the adipose expression and function of tumor necrosis factor α (TNF-α) and transforming growth factor β (TGF-β). Both TNF-α and TGF-β blocked adipose differentiation in vitro and led to a marked reduction in glycerol-3-phosphate dehydrogenase activity, a marker enzyme of adipose differentiation, by 69% ± 11% and 75% ± 15%, respectively. Addition of 2 μmol/L troglitazone significantly reduced this inhibitory effect of both cytokines on glycerol-3-phosphate dehydrogenase activity. Peroxisome proliferator–activated receptor γ messenger RNA (mRNA) was reduced by TNF-α in freshly isolated adipocytes. This effect was completely counteracted by troglitazone, whereas TGF-β had no immediate effect on peroxisome proliferator–activated receptor γ mRNA. Moreover, troglitazone alone promoted adipose differentiation in a time- and dose-dependent manner. Troglitazone treatment was found to result in a marked reduction of TNF-α mRNA expression in human preadipocytes to 54% ± 13% compared with untreated cultures. Furthermore, troglitazone was observed to partially antagonize the inhibitory effect of TNF-α on insulin-stimulated 2-deoxy-glucose uptake in newly differentiated human fat cells. In conclusion, troglitazone exerts a potent adipogenic activity in human preadipocytes, which may be mediated by suppression of the endogenous production of TNF-α and by counteracting the antiadipogenic effect of TGF-β. In addition, troglitazone improved insulin-stimulated glucose uptake in differentiated fat cells.