Department of Physiology, Monash University, Clayton, Vic., Australia.
Neuroendocrinology. 2011;93(1):48-57. doi: 10.1159/000322589. Epub 2010 Dec 1.
Ghrelin plays an important role in energy metabolism by regulating food intake, body weight and glucose homeostasis. In this review, we highlight recent developments describing how ghrelin stimulates neuropeptide Y (NPY) neurons, but not pro-opiomelanocortin neurons, to regulate food intake. We describe a novel signaling modality, in which ghrelin activates NPY/agouti-related protein (AgRP) neurons through fatty acid oxidation, reactive oxygen species buffering and mitochondrial function. We hypothesize that this unique system may serve to maintain NPY/AgRP cell function during prolonged negative energy balance. We discuss the idea that the metabolic status plays a key role in ghrelin function. For example, our recent studies illustrate that diet-induced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons. On the other side of the metabolic coin, ghrelin and GOAT knockout models show that ghrelin is required to maintain blood glucose during severe calorie restriction. We propose the hypothesis that ghrelin primarily functions during negative energy balance to maintain whole-body energy homeostasis.
胃饥饿素通过调节食物摄入、体重和葡萄糖稳态在能量代谢中发挥重要作用。在这篇综述中，我们强调了最近的研究进展，描述了胃饥饿素如何刺激神经肽 Y（NPY）神经元而不是促阿黑皮素原（POMC）神经元来调节食物摄入。我们描述了一种新的信号转导模式，其中胃饥饿素通过脂肪酸氧化、活性氧缓冲和线粒体功能激活 NPY/AgRP 神经元。我们假设，这种独特的系统可能有助于在长时间的负能平衡期间维持 NPY/AgRP 细胞功能。我们讨论了代谢状态在胃饥饿素功能中起关键作用的观点。例如，我们最近的研究表明，饮食诱导的肥胖导致弓状核 NPY/AgRP 神经元对胃饥饿素产生抵抗。另一方面，胃饥饿素和 G蛋白偶联受体 10 （GOAT）敲除模型表明，在严重的热量限制期间，胃饥饿素是维持血糖所必需的。我们提出假说，即胃饥饿素主要在负能平衡期间发挥作用，以维持全身能量稳态。
