| First Author | Kim K | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10255 | PubMed ID | 26743335 |
| Mgi Jnum | J:235815 | Mgi Id | MGI:5803751 |
| Doi | 10.1038/ncomms10255 | Citation | Kim K, et al. (2016) mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2. Nat Commun 7:10255 |
| abstractText | 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 beta-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. |
