Central administration of leptin to ovariectomized ewes inhibits food intake without affecting the secretion of hormones from the pituitary gland: Evidence for a dissociation of effects on appetite and neuroendocrine function

We have studied the effect of leptin on food intake and neuroendocrine func tion in ovariectomized ewes. Groups (n = 5) received intracerebroventricula r infusions of either vehicle or leptin (20 mu g/h) for 3 days and were blo od sampled over 6 h on days -1, 2, and for 3 h on day 3 relative to the ons et of the infusion. The animals were then killed to measure hypothalamic ne uropeptide Y expression by in situ hybridization. Plasma samples were assay ed for metabolic parameters and pituitary hormones. Food intake was reduced by leptin, but did not change in controls. Leptin treatment elevated plasm a lactate and nonesterified fatty acids, but did not affect glucose or insu lin levels, indicating a state of negative energy balance that was met by t he mobilization of body stores. Pulse analysis showed that the secretion of LH and GH was not affected by leptin treatment, nor were the mean plasma c oncentrations of FSH, PRL, or cortisol. Expression of messenger RNA for neu ropeptide Y in the arcuate nucleus was reduced by the infusion of leptin, p rimarily due to reduced expression per cell rather than a reduction in the number of cells observed. Thus, the action of leptin to inhibit food intake is dissociated from neuroendocrine function. These results suggest that th e metabolic effects of leptin are mediated via neuronal systems that posses s leptin receptors rather than via endocrine effects.