下丘脑 κ 阿片受体调节胃饥饿素的摄食作用。
Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin.
机构信息
Department of Physiology, School of Medicine-CIMUS-Instituto de Investigaciones Sanitarias (IDIS), CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), San Francisco s/n, Santiago de Compostela (A Coruña), University of Santiago de Compostela, Santiago de Compostela, Spain.
出版信息
Neuropsychopharmacology. 2013 Jun;38(7):1296-307. doi: 10.1038/npp.2013.28. Epub 2013 Jan 24.
Abstract
The opioid system is well recognized as an important regulator of appetite and energy balance. We now hypothesized that the hypothalamic opioid system might modulate the orexigenic effect of ghrelin. Using pharmacological and gene silencing approaches, we demonstrate that ghrelin utilizes a hypothalamic κ-opioid receptor (KOR) pathway to increase food intake in rats. Pharmacological blockade of KOR decreases the acute orexigenic effect of ghrelin. Inhibition of KOR expression in the hypothalamic arcuate nucleus is sufficient to blunt ghrelin-induced food intake. By contrast, the specific inhibition of KOR expression in the ventral tegmental area does not affect central ghrelin-induced feeding. This new pathway is independent of ghrelin-induced AMP-activated protein kinase activation, but modulates the levels of the transcription factors and orexigenic neuropeptides triggered by ghrelin to finally stimulate feeding. Our novel data implicate hypothalamic KOR signaling in the orexigenic action of ghrelin.
摘要
阿片系统被广泛认为是调节食欲和能量平衡的重要调节器。我们现在假设，下丘脑阿片系统可能调节胃饥饿素的食欲刺激作用。我们使用药理学和基因沉默方法，证明胃饥饿素利用下丘脑κ-阿片受体（KOR）途径增加大鼠的食物摄入。KOR 的药理学阻断会降低胃饥饿素的急性食欲刺激作用。抑制下丘脑弓状核中的 KOR 表达足以使胃饥饿素诱导的食物摄入迟钝。相比之下，腹侧被盖区中 KOR 表达的特异性抑制不会影响中枢胃饥饿素诱导的摄食。这条新途径与胃饥饿素诱导的 AMP 激活蛋白激酶激活无关，但调节了胃饥饿素触发的转录因子和食欲肽的水平，最终刺激摄食。我们的新数据表明，下丘脑 KOR 信号转导参与了胃饥饿素的食欲刺激作用。
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