Role of the Y5 neuropeptide Y receptor in feeding and obesity
Role of the Y5 neuropeptide Y receptor in feeding and obesity
复制标题
DOI：
10.1038/nm0698-718
复制
发表时间：
1998-06-01
期刊：
影响因子：
82.9
通讯作者：
Palmiter, RD
中科院分区：
文献类型：
--
作者：
Marsh, DJ;Hollopeter, G;Palmiter, RD
神经肽Y（NPY）是一种在大脑中大量表达的36个氨基酸的神经调质（1），与食物摄入和体重的调节有关（2-4）。药理学数据表明，NPY对食欲的刺激作用是由G蛋白偶联的NPY Y 5受体（5）（Y 5 R）转导的。我们已经在小鼠中灭活了Y 5 R基因，并报告说，年轻的Y 5 R基因缺失小鼠正常进食和生长;然而，它们会出现轻度的迟发性肥胖，其特征是体重增加，食物摄入量增加和肥胖。在年轻的Y 5 R基因缺失小鼠中，禁食诱导的再喂养没有变化，它们对瘦素表现出正常的敏感性。它们对脑室内（icv）给予NPY和相关肽的反应降低或不存在。神经肽Y缺乏可减轻瘦素缺乏小鼠（6）（ob/ob）的肥胖综合症，但这些作用并不是由Y 5 R的神经肽Y信号传导介导的，因为Y 5 R缺失的ob/ob小鼠同样肥胖。这些结果表明，Y 5 R有助于由中枢施用的NPY及其类似物诱导的摄食，但不是小鼠中关键的生理摄食受体。
Neuropeptide Y (NPY), a 36-amino-acid neuromodulator abundantly expressed in the brain(1), has been implicated in the regulation of food intake and body weight(2-4). Pharmacological data suggest that NPY's stimulatory effect on appetite is transduced by the G-protein-coupled NPY Y5 receptor(5) (Y5R). We have inactivated the Y5R gene in mice and report that younger Y5R-null mice feed and grow normally; however, they develop mild late-onset obesity characterized by increased body weight, food intake and adiposity. Fasting-induced refeeding is unchanged in younger Y5R-null mice and they exhibit normal sensitivity to leptin. Their response to intracerebroventricular (icv) administration of NPY and related peptides is either reduced or absent. NPY deficiency attenuates the obesity syndrome of mice deficient for leptin(6) (ob/ob), but these effects are not mediated by NPY signaling through the Y5R because Y5R-null ob/ob mice are equally obese. These results demonstrate that the Y5R contributes to feeding induced by centrally administered NPY and its analogs, but is not a critical physiological feeding receptor in mice.