DIRECT EFFECTS OF LEPTIN ON BROWN AND WHITE ADIPOSE-TISSUE

Leptin is thought to exert its actions on energy homeostasis through t he long form of the leptin receptor (OB-Rb), which is present in the h ypothalamus and in certain peripheral organs, including adipose tissue . In this study, we examined whether leptin has direct effects on the function of brown and white adipose tissue (BAT and WAT, respectively) at the metabolic and molecular levels, The chronic peripheral intrave nous administration of leptin in vivo for 4 d resulted in a 1.6-fold i ncrease in the in vivo glucose utilization index of EAT, whereas no si gnificant change was found after intracerebroventricular administratio n compared with pair-fed control rats, compatible with a direct effect of leptin on BAT, The effect of leptin on WAT fat pads from lean Zuck er Fal fa rats was assessed ex vivo, where a 9- and 16-fold increase i n the rate of lipolysis tvas observed after 2 h of exposure to 0.1 and 10 nM leptin, respectively, In contrast, no increase in Lipolysis was observed in the fat pads from obese fa/fa rats, which harbor an inact ivating mutation in the OB-Rb. At the level of gene expression, leptin treatment for 24 h increased malic enzyme acid lipoprotein lipase RNA 1.8 +/- 0.17 and 1.9 +/- 0.14-fold, respectively, while aP2 mRNA leve ls were unaltered in primary cultures of brown adipocytes from lean Fa /fa rats. Importantly, however, no significant effect of leptin was ob served on these genes in brown adipocytes from obese fa/fa animals, Th e presence of OB-Rb receptors in adipose tissue was substantiated by t he detection of its transcripts by RT-PCR, and leptin treatment in viv o and in vitro activated the specific STATs implicated in the signalin g pathway of the OB-Rb. Taken together, our data strongly suggest that leptin has direct effects on BAT and WAT, resulting in the activation of the Jak/STAT pathway and the increased expression of certain targe t genes, which may partially account for the observed increase in gluc ose utilization and lipolysis in leptin-treated adipose tissue.