NEUROPEPTIDE-Y SECRETION INCREASES IN THE PARAVENTRICULAR NUCLEUS IN ASSOCIATION WITH INCREASED APPETITE FOR FOOD
NEUROPEPTIDE-Y SECRETION INCREASES IN THE PARAVENTRICULAR NUCLEUS IN ASSOCIATION WITH INCREASED APPETITE FOR FOOD
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DOI：
10.1073/pnas.88.23.10931
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
KALRA, PS
中科院分区：
文献类型：
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作者：
KALRA, SP;DUBE, MG;KALRA, PS
哺乳动物的进食是一种周期性行为；然而，对大脑如何发出间歇性进食模式的信息知之甚少。最近的间接证据表明，神经肽Y(NPY)结构中编码的信号之一是刺激强健的摄食。因此，进行了两个系列的实验，以表征大鼠室旁核(PVN)内NPY分泌与进食行为的关系。在每日进食4h的训练大鼠进食前和进食过程中，观察下丘脑多个部位NPY浓度和下丘脑室旁核(PVN)NPY释放的动态变化，发现只有PVN的NPY浓度在进食前升高，此后在进食过程中显著下降。在不受束缚的大鼠中，通过推拉套管灌流收集的样本中，NPY释放到PVN间质中的时间模式类似。此外，在表现出强烈摄食动力的食物剥夺大鼠中，PVN中NPY的释放也以高幅度分泌发作的形式显著增加，而在自由进食的大鼠中，NPY的释放速度较低。自由进食2 4h后，空腹大鼠NPY释放率恢复到对照组水平。这些发现表明，在下丘脑的一个离散部位内，NPY神经分泌活动强烈而动态，并伴随着食物消费冲动的增加，这表明PVN中NPY的释放是周期性进食行为的一个重要的食欲信号。这些结果对于阐明神经性厌食症、暴食症和肥胖症等进食障碍的病理生理学的根本原因，以及构建用于治疗干预的合适的NPY受体激动剂和拮抗剂的制定和测试的特定上下文模型具有重要的全球意义。
Feeding in mammals is a periodic behavior; however, knowledge of how the brain signals an intermittent eating pattern is scanty. Recent indirect evidence indicates that one of the signals encoded in the structure of neuropeptide Y (NPY) is to stimulate robust feeding. Therefore, two series of experiments were undertaken to characterize NPY secretion within the paraventricular nucleus (PVN) in association with eating behavior in the rat. Dynamic changes in NPY concentration in several hypothalamic sites and release in the PVN were assessed before and during the course of food consumption in rats trained to eat daily only for 4 h. Only in the PVN were NPY concentrations elevated before the introduction of food and, thereafter, levels decreased significantly during the course of eating. A similar temporal pattern in NPY release into the PVN interstitium was evident in samples collected by push-pull cannula perfusion in unrestrained rats. In addition, in food-deprived rats displaying a robust drive for feeding, NPY release in the PVN was also markedly enhanced in the shape of high-amplitude secretory episodes as compared to a lower release rate in rats receiving food ad libitum. The higher rate of NPY release in fasted rats returned to the control range after 24 h of ad libitum food supply. These findings of intense and dynamic NPY neurosecretory activity within a discrete hypothalamic site in association with an increased drive for food consumption demonstrate that NPY release in the PVN is an important orexigenic signal for periodic eating behavior. These results have important global implications for elucidating the underlying causes of the pathophysiology of eating disorders-anorexia nervosa, bulimia, and obesity-as well as constituting a specific contextual model for the formulation and testing of suitable NPY receptor agonists and antagonists for therapeutic intervention.