PPARγ-induced upregulation of subcutaneous fat adiponectin secretion, glyceroneogenesis and BCAA oxidation requires mTORC1 activity
Autor: | Juliana Magdalon, Maynara L. Andrade, Mayara Franzoi Moreno, Milene Ortiz-Silva, Patricia Chimin, Sayuri Miyamoto, Thayna S. Vieira, Tiago E. Oliveira, Luiz Augusto Perandini, Rachael Ivison, Deepti Pant, Adriano B. Chaves-Filho, Érique Castro, Linus T.-Y. Tsai, Albert S. Peixoto, William T. Festuccia, Caroline A. Thomazelli, Marcos Yukio Yoshinaga, Thiago Belchior, Gustavo R. Gilio |
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Rok vydání: | 2021 |
Předmět: |
Glycerol
0301 basic medicine medicine.medical_specialty Subcutaneous Fat 030209 endocrinology & metabolism mTORC1 White adipose tissue Mechanistic Target of Rapamycin Complex 1 Article Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Adipocyte Internal medicine medicine Glyceroneogenesis Animals Adiponectin secretion Molecular Biology Adiponectin Cell Biology Up-Regulation PPAR gamma FISIOLOGIA 030104 developmental biology Endocrinology chemistry Rosiglitazone Oxidation-Reduction Amino Acids Branched-Chain medicine.drug |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Biochim Biophys Acta Mol Cell Biol Lipids |
ISSN: | 1388-1981 |
Popis: | The nutrient sensors peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ 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 PPARγ 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 PPARγ activation with rosiglitazone. Mechanistically, adipocyte mTORC1 deficiency impairs PPARγ transcriptional activity by reducing PPARγ protein content, as well as by downregulating C/EBPα, a co-partner and facilitator of PPARγ. In conclusion, mTORC1 and PPARγ are essential partners involved in the regulation of subcutaneous adipose tissue adiponectin production and secretion and BCAA oxidative metabolism. |
Databáze: | OpenAIRE |
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