Evidence that neurotensin mediates the central effect of leptin on food intake in rat.

Evidence that neurotensin mediates the central effect of leptin on food intake in rat.
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神经降压素介导瘦素对大鼠食物摄入的中枢作用的证据。

DOI:
10.1016/s0006-8993(00)03107-3
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发表时间:
2001
期刊:
影响因子:
2.9
通讯作者:
Wang,YP
Wang,YP
中科院分区:
医学3区
文献类型:
--
作者:
Sahu,A;Carraway,RE;Wang,YP

文献摘要

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最近的证据表明,瘦素对食物摄入和体重调节的作用是由下丘脑中的许多食欲和厌食神经元系统介导的。我们以前的研究表明,中枢注射瘦素诱导下丘脑神经降压素(NT)基因表达与大鼠摄食量减少和体重减轻相关,这表明NT是一种厌食肽,参与介导瘦素对摄食和体重调节的作用。为了开始检查NT在这方面的相对作用,我们评估了NT抗血清(NT-AS)或NT受体拮抗剂SR 48692对大鼠中瘦素饱腹感作用的影响。在第一个实验中,第三脑室(i.c.v.)在注射瘦素(4 μ g)前30 min给予NT-AS 1或5 μ l,可完全阻断瘦素对食物剥夺(FD)诱导的摄食的影响。在第二个实验中,腹膜内(i.p.)SR 48692(40 μ g/kg)的给药也完全阻止了瘦素对FD诱导的进食的饱腹作用。这些结果表明,无论是NT免疫中和或NT-受体拮抗作用的逆转瘦素的饱腹感的行动支持我们的假设,NT参与介导瘦素的行动喂养,并进一步表明,这种神经肽是一个定量的重要组成部分的瘦素敏感的神经回路。
Recent evidence suggests that leptin’s action on food intake and body weight regulation is mediated by a number of orexigenic and anorectic neuronal systems in the hypothalamus. Our previous demonstration that central injections of leptin induce hypothalamic neurotensin (NT) gene expression in association with a reduced food intake and decreased body weight in rats indicates that NT, an anorectic peptide, is involved in mediating leptin’s action on feeding and body weight regulation. To begin to examine the relative role of NT in this regard we evaluated the effects of NT antiserum (NT-AS) or NT receptor antagonist, SR 48692, on the satiety action of leptin in rats. In the first experiment, 3rd cerebroventricular (i.c.v.) administration of either 1 or 5 μl of NT-AS, 30 min prior to leptin (4 μg) injection, completely blocked the effects of leptin on food deprivation (FD)-induced feeding. In the second experiment, intraperitoneal (i.p.) administration of SR 48692 (40 μg/kg) also completely prevented leptin’s satiety action on FD-induced feeding. These results showing the reversal of leptin’s satiety action by either NT immunoneutralization or NT-receptor antagonism support our hypothesis that NT is involved in mediating leptin’s action on feeding and further suggest that this neuropeptide is a quantitatively important component of the leptin sensitive neural circuitry.