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

Asai, Masato ; Ramachandrappa, Shwetha ; Joachim, Maria ; Shen, Yuan ; Zhang, Rong ; Nuthalapati, Nikhil ; Ramanathan, Visali ; Strochlic, David E. ; Ferket, Peter and Linhart, Kirsten , et al. (2013) In Science 341(6143). p.275-278
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science
volume
341
issue
6143
pages
275 - 278
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • wos:000321959300043
  • scopus:84880438580
  • pmid:23869016
ISSN
1095-9203
DOI
10.1126/science.1233000
language
English
LU publication?
yes
id
e9e444f6-33e8-4631-93af-73dddcdc04ce (old id 3973381)
date added to LUP
2016-04-01 13:57:34
date last changed
2022-04-22 00:32:48
@article{e9e444f6-33e8-4631-93af-73dddcdc04ce,
  abstract     = {{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       = {{Asai, Masato and Ramachandrappa, Shwetha and Joachim, Maria and Shen, Yuan and Zhang, Rong and Nuthalapati, Nikhil and Ramanathan, Visali and Strochlic, David E. and Ferket, Peter and Linhart, Kirsten and Ho, Caroline and Novoselova, Tatiana V. and Garg, Sumedha and Ridderstråle, Martin and Marcus, Claude and Hirschhorn, Joel N. and Keogh, Julia M. and O'Rahilly, Stephen and Chan, Li F. and Clark, Adrian J. and Farooqi, I. Sadaf and Majzoub, Joseph A.}},
  issn         = {{1095-9203}},
  language     = {{eng}},
  number       = {{6143}},
  pages        = {{275--278}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science}},
  title        = {{Loss of Function of the Melanocortin 2 Receptor Accessory Protein 2 Is Associated with Mammalian Obesity}},
  url          = {{http://dx.doi.org/10.1126/science.1233000}},
  doi          = {{10.1126/science.1233000}},
  volume       = {{341}},
  year         = {{2013}},
}