Sympathetic activation of leptin via the ventromedial hypothalamus - Leptin-induced increase in catecholamine secretion

Leptin is an adipocyte-derived blood-borne satiety factor that acts directl y on the hypothalamus, thereby regulating food intake and energy expenditur e. We have demonstrated that the hypothalamic arcuate nucleus (Arc) is a pr imary site of the satiety effect of leptin (Neurosci Lett 224:149-152, 1997 ), To explore the hypothalamic pathway of sympathetic activation of leptin, we examined the effects of a single intravenous or intracerebroventricular injection of recombinant human leptin on catecholamine secretion in rats. We also examined the effects of direct microinjection of leptin into the ve ntromedial hypothalamus (VMH), Are, paraventricular nucleus (PVN), and dors omedial hypothalamus (DMH) in rats. To further assess whether sympathetic a ctivation of leptin is mediated via the VMH, we also examined the effects o f a single intravenous injection of leptin in VMH-lesioned rats. A single i njection of leptin (0.25-1.0 mg i.v./rat or 0.5-2.0 mu g i.c.v./rat) increa sed plasma norepinephrine (NE) and epinephrine (EPI) concentrations in a do se-dependent manner. Plasma NE and EPI concentrations were increased signif icantly when leptin was injected directly into the VMH but were unchanged w hen injected into the Are, PVN, and DMH, Plasma NE and EPI concentrations w ere unchanged in VMH-lesioned rats that received a single intravenous injec tion of leptin. The present study provides evidence that a leptin-induced i ncrease in catecholamine secretion is mediated primarily via the VMH and su ggests the presence of distinct hypothalamic pathways mediating the satiety effect and sympathetic activation of leptin.