期刊
SCIENCE
卷 341, 期 6143, 页码 275-278出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1233000
关键词
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资金
- National Institutes of Health [NIHP30-HD18655]
- Timothy Murphy Fund
- National Alliance for Research on Schizophrenia and Depression
- Wellcome Trust
- Medical Research Council [G0802796]
- NIHR Cambridge Biomedical Research Centre
- Pfizer
- Correlagen Diagnostics
- [R01DK075787]
- Medical Research Council [MC_UU_12012/5/B, G0600717B, G9824984, G0802796, MC_UU_12012/1, G0900554, G0600717] Funding Source: researchfish
- Novo Nordisk Fonden [NNF11OC1014660] Funding Source: researchfish
- MRC [G9824984, G0600408, G0802796, G0900554, MC_UU_12012/1, G0600717] Funding Source: UKRI
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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