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
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
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DOI：
10.1210/en.140.3.1175
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发表时间：
1999-03-01
期刊：
影响因子：
4.8
通讯作者：
Clarke, IJ
中科院分区：
文献类型：
--
作者：
Henry, BA;Goding, JW;Clarke, IJ
本实验研究了瘦素对去卵巢母羊摄食量和神经内分泌功能的影响。各组(n=5)采用侧脑室注射赋形剂或瘦素(20mgh)，连续3d，第1、2天采血6h以上，第3天采血3h。然后处死动物，用原位杂交法检测下丘脑神经肽Y的表达。测定血浆代谢参数和脑垂体激素水平。瘦素减少了食物摄入量，但对照组的摄入量没有变化。瘦素治疗提高了血浆乳酸和非酯化脂肪酸水平，但不影响血糖或胰岛素水平，表明身体储备的动员满足了负能量平衡状态。脉搏分析显示，瘦素治疗不影响促黄体生成素和生长激素的分泌，也不影响FSH、PRL和皮质醇的平均浓度。注射瘦素可减少弓状核神经肽Y信使RNA的表达，主要是由于每个细胞的表达减少，而不是观察到的细胞数量减少。因此，瘦素抑制食物摄取的作用与神经内分泌功能是分离的。这些结果表明，瘦素的代谢作用是通过具有瘦素受体的神经系统而不是内分泌作用来调节的。
We have studied the effect of leptin on food intake and neuroendocrine function in ovariectomized ewes. Groups (n = 5) received intracerebroventricular infusions of either vehicle or leptin (20 mu g/h) for 3 days and were blood sampled over 6 h on days -1, 2, and for 3 h on day 3 relative to the onset of the infusion. The animals were then killed to measure hypothalamic neuropeptide Y expression by in situ hybridization. Plasma samples were assayed for metabolic parameters and pituitary hormones. Food intake was reduced by leptin, but did not change in controls. Leptin treatment elevated plasma lactate and nonesterified fatty acids, but did not affect glucose or insulin levels, indicating a state of negative energy balance that was met by the 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 concentrations of FSH, PRL, or cortisol. Expression of messenger RNA for neuropeptide Y in the arcuate nucleus was reduced by the infusion of leptin, primarily 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 the metabolic effects of leptin are mediated via neuronal systems that possess leptin receptors rather than via endocrine effects.