Loss of Function of the Melanocortin 2 Receptor Accessory Protein 2 Is Associated with Mammalian Obesity

Summary, in English

Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin receptors in vitro. To investigate the physiological role of brain-expressed melanocortin 2 receptor accessory protein 2 (MRAP2), we characterized mice with whole-body and brain-specific targeted deletion of Mrap2, both of which develop severe obesity at a young age. Mrap2 interacts directly with melanocortin 4 receptor (Mc4r), a protein previously implicated in mammalian obesity, and it enhances Mc4r-mediated generation of the second messenger cyclic adenosine monophosphate, suggesting that alterations in Mc4r signaling may be one mechanism underlying the association between Mrap2 disruption and obesity. In a study of humans with severe, early-onset obesity, we found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans.

• Author: Masato Asai; Shwetha Ramachandrappa; Maria Joachim; Yuan Shen; Rong Zhang; Nikhil Nuthalapati; Visali Ramanathan; David E. Strochlic; Peter Ferket; Kirsten Linhart; Caroline Ho; Tatiana V. Novoselova; Sumedha Garg; Martin Ridderstråle; Claude Marcus; Joel N. Hirschhorn; Julia M. Keogh; Stephen O'Rahilly; Li F. Chan; Adrian J. Clark; I. Sadaf Farooqi; Joseph A. Majzoub
• Department/s: Diabetes - Clinical Obesity; EXODIAB: Excellence of Diabetes Research in Sweden
• Publishing year: 2013
• Language: English
• Pages: 275-278
• Publication/Series: Science
• Volume: 341
• Issue: 6143
• Links: http://dx.doi.org/10.1126/science.1233000
• Document type: Journal article
• Publisher: American Association for the Advancement of Science (AAAS)
• Topic: Nutrition and Dietetics
• Status: Published
• Research group: Diabetes - Clinical Obesity
• ISBN/ISSN/Other: ISSN: 1095-9203