The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis
The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis
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DOI：
10.1016/s0896-6273(03)00063-1
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发表时间：
2003-02-20
期刊：
影响因子：
16.2
通讯作者：
Horvath, TL
中科院分区：
文献类型：
--
作者：
Cowley, MA;Smith, RG;Horvath, TL
胃肠肽激素胃饥饿素通过下丘脑的作用刺激啮齿动物和人类的食欲。我们在第三脑室附近的一组神经元中发现了ghrelin的表达，这些神经元位于下丘脑背核、腹核、室旁核和弓形核之间。这些神经元向下丘脑的关键回路发送输出信号，包括产生神经肽Y （NPY）、agouti相关蛋白（AGRP）、促黑素原（POMC）产物和促肾上腺皮质激素释放激素（CRH）的回路。在下丘脑内，胃饥饿素主要结合在NPY神经元的突触前末端。通过电生理记录，我们发现胃饥饿素刺激弓形NPY神经元的活动，并模拟了NPY在下丘脑室旁核（PVH）中的作用。我们认为，在这些位点，胃饥饿素的释放可能会刺激促氧肽和神经递质的释放，从而代表了一种控制能量稳态的新调控回路。
The gastrointestinal peptide hormone ghrelin stimulates appetite in rodents and humans via hypothalamic actions. We discovered expression of ghrelin in a previously uncharacterized group of neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These neurons send efferents onto key hypothalamic circuits, including those producing neuropeptide Y (NPY), Agouti-related protein (AGRP), proopiomelanocortin (POMC) products, and corticotropin-releasing hormone (CRH). Within the hypothalamus, ghrelin bound mostly on presynaptic terminals of NPY neurons. Using electrophysiological recordings, we found that ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH). We propose that at these sites, release of ghrelin may stimulate the release of orexigenic peptides and neurotransmitters, thus representing a novel regulatory circuit controlling energy homeostasis.