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Publication : Hypothalamic Ahi1 mediates feeding behavior through interaction with 5-HT2C receptor.

First Author  Wang H Year  2012
Journal  J Biol Chem Volume  287
Issue  3 Pages  2237-46
PubMed ID  22123816 Mgi Jnum  J:180668
Mgi Id  MGI:5306828 Doi  10.1074/jbc.M111.277871
Citation  Wang H, et al. (2012) Hypothalamic Ahi1 mediates feeding behavior through interaction with 5-HT2C receptor. J Biol Chem 287(3):2237-46
abstractText  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(2C)R), known for its critical role in feeding and appetite control. First, we demonstrated the co-localization and interaction between hypothalamic Ahi1 and 5-HT(2C)R. Ahi1 promoted the degradation of 5-HT(2C)R through the lysosomal pathway. Then, we investigated the effects of fasting on the expression of hypothalamic Ahi1 and 5-HT(2C)R. Fasting resulted in an increased Ahi1 expression and a concomitant decreased expression of 5-HT(2C)R. Knockdown of hypothalamic Ahi1 led to a concomitant increased expression of 5-HT(2C)R 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(2C)R to modulate the serotonin signaling pathway.
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