A role for the endogenous opioid β-endorphin in energy homeostasis
A role for the endogenous opioid β-endorphin in energy homeostasis
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DOI：
10.1210/en.2002-221096
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发表时间：
2003-05-01
期刊：
影响因子：
4.8
通讯作者：
Low, MJ
中科院分区：
文献类型：
--
作者：
Appleyard, SM;Hayward, M;Low, MJ
下丘脑中的阿黑皮质素原 (POMC) 神经元是脂肪抑制激素瘦素的直接靶标，通过整合外周和中枢信息来促进能量稳态。黑皮质素和 β-内啡肽神经肽由 POMC 加工而成，并推测在轴突末端共同释放。药理学和遗传学方法的结合已证明黑皮质素对食欲和体重具有抑制作用。相反，药理学研究普遍表明阿片类药物会刺激食物摄入。在这里，我们报道了经过基因改造选择性缺乏β-内啡肽但保留正常黑皮质素信号传导的雄性小鼠，它们食欲旺盛且肥胖。此外，β-内啡肽突变型和野生型小鼠对外源性阿片类药物具有相同的促食欲反应，对非选择性阿片类药物拮抗剂纳洛酮具有相同的厌食反应，这表明β-内啡肽具有替代的内源性阿片类药物基调，可在生理上刺激进食。这些遗传数据表明，正常的摄食调节需要β-内啡肽，但是，与早期的报告表明β-内啡肽和黑皮质素对食欲的相反作用相反，我们的结果表明，内源性释放的POMC衍生肽在调节能量稳态方面存在更互补的相互作用。
Proopiomelanocortin ( POMC) neurons in the hypothalamus are direct targets of the adipostatic hormone leptin and contribute to energy homeostasis by integrating peripheral and central information. The melanocortin and beta-endorphin neuropeptides are processed from POMC and putatively coreleased at axon terminals. Melanocortins have been shown by a combination of pharmacological and genetic methods to have inhibitory effects on appetite and body weight. In contrast, pharmacological studies have generally indicated that opioids stimulate food intake. Here we report that male mice engineered to selectively lack beta-endorphin, but that retained normal melanocortin signaling, were hyperphagic and obese. Furthermore, beta-endorphin mutant and wild-type mice had identical orexigenic responses to exogenous opioids and identical anorectic responses to the nonselective opioid antagonist naloxone, implicating an alternative endogenous opioid tone to beta-endorphin that physiologically stimulates feeding. These genetic data indicate that beta-endorphin is required for normal regulation of feeding, but, in contrast to earlier reports suggesting opposing actions of beta-endorphin and melanocortins on appetite, our results suggest a more complementary interaction between the endogenously released POMC-derived peptides in the regulation of energy homeostasis.