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Pubmed ID :23869016
Publication Date : //

Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity.


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.

Authors : Asai Masato , Ramachandrappa Shwetha , Joachim Maria , Shen Yuan , Zhang Rong , Nuthalapati Nikhil , Ramanathan Visali , Strochlic David E , Ferket Peter , Linhart Kirsten , Ho Caroline , Novoselova Tatiana V , Garg Sumedha , Ridderstråle Martin , Marcus Claude , Hirschhorn Joel N , Keogh Julia M , O'Rahilly Stephen , Chan Li F , Clark Adrian J , Farooqi I Sadaf , Majzoub Joseph A ,

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