RECEPTOR-MEDIATED REGIONAL SYMPATHETIC-NERVE ACTIVATION BY LEPTIN

Leptin is a peptide hormone produced by adipose tissue which acts cent rally to decrease appetite and increase energy expenditure, Although l eptin increases norepinephrine turnover in thermogenic tissues, the ef fects of leptin on directly measured sympathetic nerve activity to the rmogenic and other tissues are not known, We examined the effects of i ntravenous leptin and vehicle on sympathetic nerve activity to brown a dipose tissue, kidney, hindlimb, and adrenal gland in anesthetized Spr ague-Dawley rats. Intravenous infusion of mouse leptin over 3 h (total dose 10-1,000 mu g/kg) increased plasma concentrations of immunoreact ive murine leptin up to 50-fold. Leptin slowly increased sympathetic n erve activity to brown adipose tissue (+286+/-64% at 1,000 mu g/kg; P = 0.002). Surprisingly, leptin infusion also produced gradual increase s in renal sympathetic nerve activity (+228+/-63% at 1,000 mu g/kg; P = 0.0008). The effect of leptin on sympathetic nerve activity was dose dependent, with a threshold dose of 100 mu g/kg. Leptin also increase d sympathetic nerve activity to the hindlimb (+287+/-60%) and adrenal gland (388+/-171%), Despite the increase in overall sympathetic nerve activity, leptin did not increase arterial pressure or heart rate, Lep tin did not change plasma glucose and insulin concentrations, Infusion of vehicle did not alter sympathetic nerve activity, Obese Zucker rat s, known to possess a mutation in the gene for the leptin receptor, we re resistant to the sympathoexcitatory effects of leptin, despite high er achieved plasma leptin concentrations, These data demonstrate that leptin increases thermogenic sympathetic nerve activity and reveal an unexpected stimulatory effect of leptin on overall sympathetic nerve t raffic.