{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kim K"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS"],"pagination":["10255"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4729872"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7"],"pubmed_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 β-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"],"journal":["Nature communications"],"pubmed_title":["mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2."],"pmcid":["PMC4729872"],"funding_grant_id":["DK093604","R01 HL114949","K08 DK093604","T32 DK065522","P30 DK026687","R01 DK103818","R00 DK097455"],"pubmed_authors":["Hayden MS","Kim K","Qiang L","Sparling DP","Purcell NH","Pajvani UB"],"additional_accession":[]},"is_claimable":false,"name":"mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2.","description":"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 β-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","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Jan","modification":"2025-04-04T03:42:29.126Z","creation":"2019-03-27T02:07:44Z"},"accession":"S-EPMC4729872","cross_references":{"pubmed":["26743335"],"doi":["10.1038/ncomms10255"]}}