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, Linhart, Kirsten, Ho, Caroline, Novoselova, Tatiana ORCID logoORCID: https://orcid.org/0000-0002-2394-4667, Garg, Sumedha, Ridderstråle, Martin, Marcus, Claude, Hirschhorn, Joel N., Keogh, Julia M., O’Rahilly, Stephen, Chan, Li F., Clark, Adrian, Farooqi, Sadaf and Majzoub, Joseph A. (2013) Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science, 341 (6143) . pp. 275-278. ISSN 0036-8075 [Article] (doi:10.1126/science.1233000)

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 AMP, 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

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 28132
Useful Links:
Depositing User: Tatiana Novoselova
Date Deposited: 11 Nov 2019 17:47
Last Modified: 11 Nov 2019 18:36
URI: https://eprints.mdx.ac.uk/id/eprint/28132

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