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

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

  • Science. 2013 Jul 19;341(6143):275-8. doi: 10.1126/science.1233000.
Masato Asai 1,  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
Affiliations

Affiliation

  • 1 Division of Endocrinology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
PMID: 23869016 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 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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