Shioda Seiji, Takenoya Fumiko, Yagi Michiko, Wang Lihua, Hori Yasunori, Kageyama Haruaki
Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
Nutrition. 2008 Sep;24(9):848-53. doi: 10.1016/j.nut.2008.06.016.
Novel neuropeptides acting as G-protein-coupled receptor (GPCR) ligands are known to be localized in the brain and play a range of physiologic functions, one of which is feeding regulation. We describe the distribution and localization of these recently identified GPCR ligands and review their involvement in neuronal networks, particularly in feeding regulation. This review addresses aspects of some novel GPCR ligands, including feeding-regulating neuropeptides such as orexin, ghrelin, and galanin-like peptide and other known neuropeptides such as neuropeptide Y and pro-opiomelanocortin. These neuropeptides have been studied by our research group and others, particularly with regard to interactions in the hypothalamus of neurons containing these neuropeptides. In the hypothalamus, cross-talk among such neurons plays a key role in determining feeding states and feeding behavior. We describe some structural and functional characteristics of these neuropeptides and summarize the known interactions between the different kinds of feeding-regulating neurons and leptin-targeting neurons in the hypothalamus. Moreover, we present a new strategy for analyzing neural circuits involving these feeding-regulating GPCR ligands in the brain, with research in this field aided by the use of transgenic mouse models. We also present our recent results that involve aspects of feeding regulation, energy homeostasis, and body temperature regulation. Research in this field will serve the important role of clarifying neurologically based causes for appetite dysfunctions and diseases and may help in establishing new therapies for patients with such conditions.
已知作为G蛋白偶联受体（GPCR）配体的新型神经肽定位于大脑并发挥一系列生理功能，其中之一是进食调节。我们描述了这些最近鉴定出的GPCR配体的分布和定位，并综述了它们在神经网络中的作用，特别是在进食调节方面。本综述探讨了一些新型GPCR配体的相关方面，包括调节进食的神经肽，如食欲素、胃饥饿素和甘丙肽样肽，以及其他已知的神经肽，如神经肽Y和阿片促黑素皮质素原。我们的研究小组和其他人员对这些神经肽进行了研究，特别是关于含有这些神经肽的神经元在下丘脑中的相互作用。在下丘脑中，此类神经元之间的相互作用在决定进食状态和进食行为方面起着关键作用。我们描述了这些神经肽的一些结构和功能特征，并总结了下丘脑中不同种类的进食调节神经元与瘦素靶向神经元之间已知的相互作用。此外，我们提出了一种分析大脑中涉及这些调节进食的GPCR配体的神经回路的新策略，该领域的研究借助转基因小鼠模型得以推进。我们还展示了我们最近在进食调节、能量稳态和体温调节方面的研究结果。该领域的研究将在阐明食欲功能障碍和疾病的神经学基础原因方面发挥重要作用，并可能有助于为患有此类病症的患者建立新的治疗方法。
