mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2.
Nat Commun
; 7: 10255, 2016 Jan 08.
Article
en En
| MEDLINE
| ID: mdl-26743335
ABSTRACT
Mechanistic target of rapamycin complex 1 (mTORC1), defined by the presence of Raptor, is an evolutionarily conserved and nutrient-sensitive regulator of cellular growth and other metabolic processes. To date, all known functions of Raptor involve its scaffolding mTOR kinase with substrate. Here we report that mTORC1-independent ('free') Raptor negatively regulates hepatic Akt activity and lipogenesis. Free Raptor levels in liver decline with age and in obesity; restoration of free Raptor levels reduces liver triglyceride content, through reduced ß-TrCP-mediated degradation of the Akt phosphatase, PHLPP2. Commensurately, forced PHLPP2 expression ameliorates hepatic steatosis in diet-induced obese mice. These data suggest that the balance of free and mTORC1-associated Raptor governs hepatic lipid accumulation, and uncover the potentially therapeutic role of PHLPP2 activators in non-alcoholic fatty liver disease.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Hepatocitos
/
Proteínas Adaptadoras Transductoras de Señales
/
Proteína Oncogénica v-akt
/
Lipogénesis
/
Enfermedad del Hígado Graso no Alcohólico
/
Hígado
/
Obesidad
Límite:
Animals
Idioma:
En
Año:
2016
Tipo del documento:
Article