Leptin and neuropeptide Y have opposing modulatory effects on nucleus of the solitary tract neurophysiological responses to gastric loads: Implications for the control of food intake
Leptin and neuropeptide Y have opposing modulatory effects on nucleus of the solitary tract neurophysiological responses to gastric loads: Implications for the control of food intake
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DOI：
10.1210/en.2002-220352
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发表时间：
2002-10-01
期刊：
影响因子：
4.8
通讯作者：
Moran, TH
中科院分区：
文献类型：
--
作者：
Schwartz, GJ;Moran, TH
瘦素是一种脂肪激素，它调节下丘脑多个信号通路的活性，参与控制食物摄入量。本实验旨在评价中枢应用瘦素或其下游介体神经肽Y(NPY)是否通过调节脑干对孤束核(NTS)进食相关反馈信号的神经生理反应而影响摄食量。2-10ml的胃负荷可剂量依赖地激活NTS神经元，而瘦素和NPY对这种负荷容量/活动关系具有相反的调节作用：瘦素显著增加NTS对胃负荷的反应，而NPY则降低胃负荷激活NTS神经元的效力和效率。这些效应可能不是由中枢给药肽的外周效应或中枢NPY或瘦素的胃动力效应所介导，因为胃负荷容量与胃负荷敏感的迷走神经传入纤维中神经生理放电频率之间的量效关系没有变化。这些数据表明了一个机械框架，用于考虑禁食和过量进食等对能量平衡的挑战如何改变进食行为。
Leptin is an adiposity hormone that modulates the activity of multiple hypothalamic signaling pathways involved in the control of food intake. The present experiments were designed to evaluate whether central administration of leptin or one of its downstream mediators, neuropeptide Y (NPY), could affect food intake by modulating the brain stem neurophysiological response to ascending meal-related feedback signals in the nucleus of the solitary tract (NTS) in anesthetized male Long-Evans rats. NTS neurons at the rostrocaudal level of the area postrema were dose-dependently activated by gastric loads ranging from 2-10 ml, and leptin and NPY had opposite modulatory effects on this load volume/activity relationship: leptin significantly increased NTS responses to gastric loads, whereas NPY reduced the potency and efficacy with which gastric loads activated NTS neurons. These effects were probably not mediated by peripheral effects of centrally administered peptides or by the gastrokinetic effects of central NPY or leptin, because the dose-response relationship between gastric load volume and neurophysiological firing rate was unchanged in gastric load-sensitive vagal afferent fibers. These data suggest a mechanistic framework for considering how feeding behavior occurring in meals is altered by challenges to energy homeostasis, such as fasting and overfeeding.