LEPTIN INDUCTION OF UCP1 GENE-EXPRESSION IS DEPENDENT ON SYMPATHETIC INNERVATION

We previously demonstrated that leptin increases uncoupling protein 1 (UCP1) and lipoprotein lipase (LPL) gene expression in brown adipose t issue (BAT) of rats. To determine whether the induction of these trans cripts is dependent on sympathetic innervation of BAT, we unilaterally surgically denervated interscapular BAT in both pair-fed and leptin ( 0.9 mg/day by infusion)-treated rats. In pair-fed rats, the level of U CP1 mRNA in the denervated BAT pad was 30-47% less than in the innerva ted pad. In the intact BAT pad, leptin administration increased UCP1 m RNA levels by nearly 2.5-fold compared with pair-fed rats. In contrast , in the denervated BAT pad, there was no increase in UCP1 gene expres sion. When LPL mRNA was examined in pair-fed rats, there was no differ ence between innervated and denervated BAT pads. With leptin administr ation, LPL gene expression increased by 75% in both the innervated and denervated BAT pads. beta(3)-Adrenergic receptor mRNA was unaffected by either denervation or leptin, whereas uncoupling protein 2 mRNA lev els were increased in epididymal white adipose tissue (WAT) but not in perirenal WAT. CGP-12177, a specific beta(3)-adrenergic receptor agon ist, induced nearly a fourfold increase in UCP1 and a twofold increase in LPL gene expression in both the innervated and denervated BAT pads . These data indicate that the leptin induction of UCP1 gene expressio n in BAT is dependent on sympathetic innervation but that the leptin i nduction of LPL gene expression is not.