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

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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.


  • Masato Asai
  • 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
  • Claude Marcus
  • Joel N. Hirschhorn
  • Julia M. Keogh
  • Stephen O'Rahilly
  • Li F. Chan
  • Adrian J. Clark
  • I. Sadaf Farooqi
  • Joseph A. Majzoub
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Nutrition and Dietetics
Original languageEnglish
Pages (from-to)275-278
Issue number6143
Publication statusPublished - 2013
Publication categoryResearch