Central leptin and resistin combined elicits enhanced central effects on renal sympathetic nerve activity

Leptin and resistin act centrally to increase renal sympathetic nerve activity (RSNA). We investigated whether resistin and leptin combined could induce a greater response than each alone. MAP, HR and RSNA were recorded before and for 3 hours after intracerebroventricular saline (control) (n = 5), leptin (7 μg; n = 5), resistin (7 μg; n = 4) and leptin administered 15 min after resistin (n = 6). Leptin alone and resistin alone significantly increased RSNA (74±17%, 50±14% respectively) (P < 0.0001 compared to saline). When leptin and resistin were combined there was a significantly greater increase in RSNA (163±23%) compared to either drug alone (P < 0.0001). Maximum responses in MAP and HR were not significantly different between groups. We also used Fos protein to quantify the number of activated neurons in the brain. Compared to controls, there were significant increases in numbers of Fos-positive neurons (i) in the arcuate and hypothalamic paraventricular nuclei when leptin or resistin were administered alone, or combined, and (ii) in the lamina terminalis when leptin or resistin were combined. Only in the arcuate nucleus was the increase significantly greater compared to either drug alone. The findings show that leptin and resistin, combined, induces (i) a greater RSNA increase, and (ii) a greater number of activated neurons in the arcuate nucleus, than with either drug alone. Since leptin makes an important contribution to the elevated RSNA observed in obese/overweight conditions, the increased levels of leptin and resistin may mean the contribution of leptin to the elevated RSNA in those conditions is enhanced.