| First Author | Andrade ML | Year | 2021 |
| Journal | Biochim Biophys Acta Mol Cell Biol Lipids | Volume | 1866 |
| Issue | 8 | Pages | 158967 |
| PubMed ID | 34004356 | Mgi Jnum | J:312097 |
| Mgi Id | MGI:6711874 | Doi | 10.1016/j.bbalip.2021.158967 |
| Citation | Andrade ML, et al. (2021) PPARgamma-induced upregulation of subcutaneous fat adiponectin secretion, glyceroneogenesis and BCAA oxidation requires mTORC1 activity. Biochim Biophys Acta Mol Cell Biol Lipids 1866(8):158967 |
| abstractText | The nutrient sensors peroxisome proliferator-activated receptor gamma (PPARgamma) and mechanistic target of rapamycin complex 1 (mTORC1) closely interact in the regulation of adipocyte lipid storage. The precise mechanisms underlying this interaction and whether this extends to other metabolic processes and the endocrine function of adipocytes are still unknown. We investigated herein the involvement of mTORC1 as a mediator of the actions of the PPARgamma ligand rosiglitazone in subcutaneous inguinal white adipose tissue (iWAT) mass, endocrine function, lipidome, transcriptome and branched-chain amino acid (BCAA) metabolism. Mice bearing regulatory associated protein of mTOR (Raptor) deletion and therefore mTORC1 deficiency exclusively in adipocytes and littermate controls were fed a high-fat diet supplemented or not with the PPARgamma agonist rosiglitazone (30 mg/kg/day) for 8 weeks and evaluated for iWAT mass, lipidome, transcriptome (Rnaseq), respiration and BCAA metabolism. Adipocyte mTORC1 deficiency not only impaired iWAT adiponectin transcription, synthesis and secretion, PEPCK mRNA levels, triacylglycerol synthesis and BCAA oxidation and mRNA levels of related proteins but also completely blocked the upregulation in these processes induced by pharmacological PPARgamma activation with rosiglitazone. Mechanistically, adipocyte mTORC1 deficiency impairs PPARgamma transcriptional activity by reducing PPARgamma protein content, as well as by downregulating C/EBPalpha, a co-partner and facilitator of PPARgamma. In conclusion, mTORC1 and PPARgamma are essential partners involved in the regulation of subcutaneous adipose tissue adiponectin production and secretion and BCAA oxidative metabolism. |
