Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity.
Science
; 341(6143): 275-8, 2013 Jul 19.
Article
em En
| MEDLINE
| ID: mdl-23869016
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peso Corporal
/
Proteínas de Transporte
/
Receptor Tipo 4 de Melanocortina
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Proteínas Modificadoras da Atividade de Receptores
/
Obesidade
Tipo de estudo:
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Animals
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Child
/
Child, preschool
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Female
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Humans
/
Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article