Higuchi Hiroshi, Niki Takeshi, Shiiya Tomohiro
Division of Pharmacology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.
World J Gastroenterol. 2008 Nov 7;14(41):6312-7. doi: 10.3748/wjg.14.6312.
Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexigenic neuropeptides such as alpha-melatonin stimulating hormone (MSH) and cocaine-amphetamine-regulated transcript (CART) are also involved in central feeding regulation. During fasting, NPY and AgRP gene expressions are up-regulated and POMC and CART gene expressions are down-regulated in hypothalamus. Based on the network of peptidergic neurons, the former are involved in positive feeding regulation, and the latter are involved in negative feeding, which exert these feeding-regulated peptides especially in paraventricular nucleus (PVN). To clarify the compensatory mechanism of knock-out of NPY system on feeding, change in gene expressions of appetite-related neuropeptides and the feeding behavior was studied in NPY Y5-KO mice. Food intake was increased in Y5-KO mice. Fasting increased the amounts of food and water intake in the KO mice more profoundly. These data indicated the compensatory phenomenon of feeding behavior in Y5-KO mice. RT-PCR and ISH suggested that the compensation of feeding is due to change in gene expressions of AgRP, CART and POMC in hypothalamus. Thus, these findings indicated that the compensatory mechanism involves change in POMC/CART gene expression in arcuate nucleus (ARC). The POMC/CART gene expression is important for central compensatory regulation in feeding behavior.
神经肽Y（NPY）是一种强效的进食神经递质。除了NPY之外，促食欲神经肽如刺鼠相关蛋白（AgRP），以及抑食欲神经肽如α-促黑素细胞激素（MSH）和可卡因-苯丙胺调节转录物（CART）也参与中枢性进食调节。在禁食期间，下丘脑NPY和AgRP基因表达上调，而POMC和CART基因表达下调。基于肽能神经元网络，前者参与正向进食调节，后者参与负向进食调节，这些进食调节肽尤其在下丘脑室旁核（PVN）发挥作用。为了阐明NPY系统敲除对进食的代偿机制，对NPY Y5基因敲除小鼠食欲相关神经肽的基因表达变化和进食行为进行了研究。Y5基因敲除小鼠的食物摄入量增加。禁食使基因敲除小鼠的食物和水摄入量增加得更显著。这些数据表明Y5基因敲除小鼠存在进食行为的代偿现象。逆转录-聚合酶链反应（RT-PCR）和原位杂交（ISH）表明，进食的代偿是由于下丘脑AgRP、CART和POMC基因表达的变化。因此，这些发现表明代偿机制涉及弓状核（ARC）中POMC/CART基因表达的变化。POMC/CART基因表达对进食行为的中枢代偿调节很重要。
