Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake
Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake
复制标题
DOI：
10.1016/j.cmet.2015.10.012
复制
发表时间：
2015-12-01
期刊：
影响因子：
29
通讯作者：
Friedman, Jeffrey Michael
中科院分区：
文献类型：
--
作者：
Li, Zhiying;Kelly, Leah;Friedman, Jeffrey Michael
本文对下丘脑胰淀素的体内、外功能进行了研究。对下丘脑神经元的分析显示，胰岛淀粉样多肽（Iapp，胰淀素的前体）在外侧下丘脑、弓状核、内侧视前区和其他地方的神经元中表达。ob/ob小鼠下丘脑lapp的表达显著降低，外源性瘦素使其恢复正常。在切片中，胰淀素和瘦素对外侧下丘脑瘦素受体ObRb表达神经元具有相似的电生理作用，而胰淀素拮抗剂AC 187抑制其活性并减弱瘦素的作用。最后，AC 187的i. c. v.输注急性减少瘦素的厌食作用。这些数据表明，下丘脑胰淀素的转录调节瘦素，它可以直接作用于ObRb神经元与瘦素，它调节进食。这些发现为美曲瘦素/普兰林肽联合治疗肥胖症的疗效增加提供了潜在的机制。
In this report we evaluated the functions of hypothalamic amylin in vivo and in vitro. Profiling of hypothalamic neurons revealed that islet amyloid polypeptide (Iapp, precursor to amylin) is expressed in neurons in the lateral hypothalamus, arcuate nucleus, medial preoptic area, and elsewhere. Hypothalamic expression of lapp is markedly decreased in ob/ob mice and normalized by exogenous leptin. In slices, amylin and leptin had similar electrophysiologic effects on lateral hypothalamic leptin receptor ObRb-expressing neurons, while the amylin antagonist AC187 inhibited their activity and blunted the effect of leptin. Finally, i.c.v. infusion of AC187 acutely reduced the anorectic effects of leptin. These data show that hypothalamic amylin is transcriptionally regulated by leptin, that it can act directly on ObRb neurons in concert with leptin, and that it regulates feeding. These findings provide a potential mechanism for the increased efficacy of a metreleptin/pramlintide combination therapy for obesity.