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 tissue (BAT) of rats. To determine whether the induction of these transcripts 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 UCP1 mRNA in the denervated BAT pad was 30-47% less than in the innervated pad. In the intact BAT pad, leptin administration increased UCP1 mRNA 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 expression. When LPL mRNA was examined in pair-fed rats, there was no difference between innervated and denervated BAT pads. With leptin administration, LPL gene expression increased by 75% in both the innervated and denervated BAT pads. beta3-Adrenergic receptor mRNA was unaffected by either denervation or leptin, whereas uncoupling protein 2 mRNA levels were increased in epididymal white adipose tissue (WAT) but not in perirenal WAT. CGP-12177, a specific beta3-adrenergic receptor agonist, 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 expression in BAT is dependent on sympathetic innervation but that the leptin induction of LPL gene expression is not.