Hypothalamic Ahi1 Mediates Feeding Behavior through Interaction with 5-HT2C Receptor

• Type of Material: Article
• Authors: Hao Wang, Chinese Academy of Sciences; Zhenbo Huang, Chinese Academy of Sciences; Liansha Huang, Beijing University of Chinese Medicine; Shaona Niu, Linyi People's Hospital; Xiurong Rao, Chinese Academy of Sciences; Jing Xu, Chinese Academy of Sciences; Hui Kong, Chinese Academy of Sciences; Jianzhong Yang, Red Cross Hospital of Yunnan Province; Chuan Yang, Sun Yat-Sen University; Donghai Wu, Chinese Academy of Sciences; Shihua Li, Emory University; Xiao-Jiang Li, Emory University; Tonghua Liu, Beijing University of Chinese Medicine; Guoqing Sheng, Chinese Academy of Sciences
• Language: English
• Date: 2012-01-13
• Publisher: American Society for Biochemistry and Molecular Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1074/jbc.M111.277871
• Title of Journal or Parent Work: Journal of Biological Chemistry
• ISSN: 0021-9258
• Volume: 287
• Issue: 3
• Start Page: 2237
• End Page: 2246
• Grant/Funding Information: This work was also supported by National Natural Science Foundation of China (NSFC) Grants 30700213 and 30811120429; Guangdong Natural Science Foundation (GDSF) Grant 07007215; and “973” Projects 2007CB947804 and 2010CB945503 (to G. S.); and by International Traditional Chinese Medicine Program for Cooperation in Science and Technology (ISCP) Grant 2011DFA30920 (to T. L.).; This work was supported, in whole or in part, by National Institutes of Health Grant NS036232 (to X.-J. L).
• Keywords: Science & Technology; NEUROPEPTIDE-Y CONCENTRATIONS; MELANOCYTE-STIMULATING HORMONE; JOUBERT-SYNDROME; GENE-MUTATIONS; PARAVENTRICULAR NUCLEUS; MELANOCORTIN RECEPTORS; BODY-WEIGHT; FOOD-INTAKE; Life Sciences & Biomedicine; OLANZAPINE TREATMENT; ENERGY-BALANCE; Biochemistry & Molecular Biology
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Genetics

Abstract

It is indicated that there are important molecules interacting with brain nervous systems to regulate feeding and energy balance by influencing the signaling pathways of these systems, but relatively few of the critical players have been identified. In the present study, we provide the evidence for the role of Abelson helper integration site 1 (Ahi1) protein as a mediator of feeding behavior through interaction with serotonin receptor 2C (5-HT 2CR), known for its critical role in feeding and appetite control. First, we demonstrated the co-localization and interaction between hypothalamic Ahi1 and 5-HT 2CR. Ahi1 promoted the degradation of 5-HT 2CR through the lysosomal pathway. Then, we investigated the effects of fasting on the expression of hypothalamic Ahi1 and 5-HT 2CR. Fasting resulted in an increased Ahi1 expression and a concomitant decreased expression of 5-HT 2CR. Knockdown of hypothalamic Ahi1 led to a concomitant increased expression of 5-HT 2CR and a decrease of food intake and body weight. Last, we found that Ahi1 could regulate the expression of neuropeptide Y and proopiomelanocortin. Taken together, our results indicate that Ahi1 mediates feeding behavior by interacting with 5-HT 2CR to modulate the serotonin signaling pathway.