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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Nov 7, 2008; 14(41): 6312-6317
Published online Nov 7, 2008. doi: 10.3748/wjg.14.6312
Feeding behavior and gene expression of appetite-related neuropeptides in mice lacking for neuropeptide Y Y5 receptor subclass
Hiroshi Higuchi, Takeshi Niki, Tomohiro Shiiya
Hiroshi Higuchi, Takeshi Niki, Tomohiro Shiiya, Division of Pharmacology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Author contributions: Higuchi H contributed design and writing of research and Higuchi H, Niki T and Shiiya T performed research and analysis of data.
Correspondence to: Hiroshi Higuchi, MD, PhD, Professor and Chairman, Division of Pharmacology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan. hhiguchi@med.niigata-u.ac.jp
Telephone: +81-25-2272087 Fax: +81-25-2270759
Received: October 15, 2008
Revised: October 30, 2008
Accepted: November 6, 2008
Published online: November 7, 2008
Abstract

Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexigenic neuropeptides such as α-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.

Keywords: Neuropeptide Y, Y5 receptor, Feeding, Arcuate nucleus, Knockout mice