BSPED2014 Poster Presentations (1) (88 abstracts)
Melanocortin 2 receptor accessory protein 2 (Mrap2) regulates hypothalamic melanocortin-4-receptor trafficking in vivo
Tatiana Novoselova 1 , Rachel Larder 2 , Debra Rimmington 2 , Chris Lelliott 3 , Elizabeth Wynn 3 , Stephen O’Rahilly 2 , Adrian Clark 1 , Darren Logan 3 , Anthony Coll 2 & Li Chan 1
1Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, Charterhouse Square, London, UK; 2MRC Metabolic Disease Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hosp, Cambridge, UK; 3Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Recently, rare loss-of-function mutations of melanocortin-2-receptor accessory protein 2 (MRAP2) have been associated with severe, early-onset obesity in humans. In addition, whole body deletion and targeted brain specific deletion of the Mrap2 gene resulted in severe obesity in mice. In vitro data have shown Mrap2 interaction with the melanocortin-4-receptor (MC4R) affecting receptor signalling as a consequence. However, the mechanism by which Mrap2 regulates body weight in vivo is less well understood with differences between Mrap2 and Mc4r knockout (KO) mice phenotypes. In this study we show that Mrap2 complete KO mice, derived from an independent line and on two separate genetic backgrounds, have severe early obesity without detectable changes to food intake or energy expenditure. Hence, replicating recently published data. To further investigate the in vivo role of Mrap2 as a Mc4r accessory protein we used a plasma membrane enrichment technique to demonstrate a reduction of hypothalamic Mc4r protein surface expression in Mrap2 KO mice compared with WT littermates. Taken together, this work corroborates the role of Mrap2 in obesity and confirms that, at least in part, this is due to defective central melanocortin trafficking.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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