Schwartz Gary J, Moran Timothy H
Bourne Behavioral Research Laboratory, Department of Psychiatry, WMC Cornell University, White Plains, New York 10605, USA.
Endocrinology. 2002 Oct;143(10):3779-84. doi: 10.1210/en.2002-220352.
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.
瘦素是一种肥胖激素，可调节参与食物摄入控制的多个下丘脑信号通路的活性。本实验旨在评估中枢给予瘦素或其下游介质之一神经肽Y（NPY）是否能通过调节麻醉的雄性Long-Evans大鼠孤束核（NTS）中对上升的与进餐相关的反馈信号的脑干神经生理反应来影响食物摄入。最后区 rostrocaudal 水平的 NTS 神经元被 2 - 10 毫升的胃内负荷剂量依赖性激活，瘦素和 NPY 对这种负荷量/活性关系具有相反的调节作用：瘦素显著增加 NTS 对胃内负荷的反应，而 NPY 降低胃内负荷激活 NTS 神经元的效力和效果。这些作用可能不是由中枢给予的肽的外周作用或中枢 NPY 或瘦素的胃肠动力作用介导的，因为在对胃内负荷敏感的迷走传入纤维中，胃内负荷量与神经生理放电率之间的剂量反应关系未改变。这些数据为考虑诸如禁食和过度喂养等能量稳态挑战如何改变进餐时的进食行为提供了一个机制框架。
