Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocytes

The treatment of rats and mice with leptin causes dramatic body fat reducti on and in some cases even disappearance of fat tissue. Here, Eve report the effects of leptin (10 and 100 ng.mL(-1)) on isolated rat adipocytes mainta ined for 15 h in culture. Leptin decreased the incorporation of acetate int o total lipids by 30%. A reduction in this incorporation (42%) was still ob served after the leptin-cultivated adipocytes were exposed to a supraphysio logical insulin concentration (10 000 mu U.mL(-1)). On the other hand, lept in increased acetate degradation by 69% and the maximal activity of citrate synthase by 50% in isolated adipocytes. It also increased oleate degradati on by 35 and 50% at concentrations of 10 and 100 ng.mL(-1), respectively. E ventually, leptin upregulated the uncoupling protein-2 (UCP2) mRNA level by 63% and had no effect on uncoupling protein-3 (UCP3) mRNA in isolated adip ocytes. The upregulation of UCP2 mRNA might have contributed to the stimula tion of acetate and fatty acid degradation by leptin. The peripheral effect s of leptin observed in this study are in line with the general energy diss ipating role postulated for this hormone and for UCP2. They suggest mechani sms by which adipocytes regulate their fat content by an autocrine pathway without the participation of the central nervous system.