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首页> 外文期刊>Cell metabolism >Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake
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Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake

机译：下丘脑胰岛淀粉样多肽与瘦素共同调节食物摄入量

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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.
机译：在这份报告中，我们评估了体内和体外下丘脑胰岛淀粉样多肽的功能。下丘脑神经元的分析显示，胰岛淀粉样多肽（Iapp，胰岛淀粉样多肽的前体）在下丘脑外侧，弓形核，视前内侧区域和其他地方的神经元中表达。 lapp的下丘脑表达在ob / ob小鼠中明显降低，并通过外源瘦素使其正常化。在切片中，胰岛淀粉样多肽和瘦素对表达下丘脑外侧瘦素受体ObRb的神经元具有相似的电生理作用，而胰岛淀粉样多肽拮抗剂AC187抑制其活性并减弱了瘦素的作用。最后，i.c.v。输注AC187会严重降低瘦素的厌食作用。这些数据表明，下丘脑胰岛淀粉样蛋白受瘦素转录调控，它可以与瘦素协同作用直接作用于ObRb神经元，并且可以调节进食。这些发现为美特彼肽/普兰林肽联合治疗肥胖症的疗效提高提供了可能的机制。

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