TY - JOUR
T1 - Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity
AU - Asai, Masato
AU - Ramachandrappa, Shwetha
AU - Joachim, Maria
AU - Shen, Yuan
AU - Zhang, Rong
AU - Nuthalapati, Nikhil
AU - Ramanathan, Visali
AU - Strochlic, David E.
AU - Ferket, Peter
AU - Linhart, Kirsten
AU - Ho, Caroline
AU - Novoselova, Tatiana V.
AU - Garg, Sumedha
AU - Ridderstråle, Martin
AU - Marcus, Claude
AU - Hirschhorn, Joel N.
AU - Keogh, Julia M.
AU - O'Rahilly, Stephen
AU - Chan, Li F.
AU - Clark, Adrian J.
AU - Farooqi, I. Sadaf
AU - Majzoub, Joseph A.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1233000
DO - 10.1126/science.1233000
M3 - Article
C2 - 23869016
AN - SCOPUS:84880438580
VL - 341
SP - 275
EP - 278
JO - Science
JF - Science
SN - 0036-8075
IS - 6143
ER -
