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

• 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
• Journal Title: Journal of Biological Chemistry
• Volume: Volume 287, Number 3
• Publisher: American Society for Biochemistry and Molecular Biology | 2012-01-13, Pages 2237-2246
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1074/jbc.M111.277871
• Subjects: Biology, Genetics; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; MELANOCYTE-STIMULATING HORMONE; NEUROPEPTIDE-Y CONCENTRATIONS; JOUBERT-SYNDROME; BODY-WEIGHT; FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; MELANOCORTIN RECEPTORS; OLANZAPINE TREATMENT; ENERGY-BALANCE; GENE-MUTATIONS

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.