Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8301728 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2016 | 30 Pages |
Abstract
Mechanistic target of rapamycin complex 1 (mTORC1) loss of function reduces adiposity whereas partial mTORC1 inhibition enhances fat deposition. Herein we evaluated how constitutive mTORC1 activation in adipocytes modulates adiposity in vivo. Mice with constitutive mTORC1 activation in adipocytes induced by tuberous sclerosis complex (Tsc)1 deletion and littermate controls were evaluated for body mass, energy expenditure, glucose and fatty acid metabolism, mitochondrial function, mRNA and protein contents. Adipocyte-specific Tsc1 deletion reduced visceral, but not subcutaneous, fat mass, as well as adipocyte number and diameter, phenotypes that were associated with increased lipolysis, UCP-1 content (browning) and mRNA levels of pro-browning transcriptional factors C/EBPβ and ERRα. Adipocyte Tsc1 deletion enhanced mitochondrial oxidative activity, fatty acid oxidation and the expression of PGC-1α and PPARα in both visceral and subcutaneous fat. In brown adipocytes, however, Tsc1 deletion did not affect UCP-1 content and basal respiration. Adipocyte Tsc1 deletion also reduced visceral adiposity and enhanced glucose tolerance, liver and muscle insulin signaling and adiponectin secretion in mice fed with purified low- or high-fat diet. In conclusion, adipocyte-specific Tsc1 deletion enhances mitochondrial activity, induces browning and reduces visceral adiposity in mice.
Keywords
S6KUCP-1IWATTSC1PI3KRERmTORCSREBP4E-BPLPLNEFAPGCSDHBIBATERRUCPPRDM16IRSyin yangPPARHFDmechanistic target of rapamycin complexGTTPPARγ coactivatortuberous sclerosis complex 1RWATmTORRetroperitoneal White adipose tissueCYC1eukaryotic initiation factor 4E-binding proteinC/EBPS6 kinaseNon-esterified fatty acidinsulin receptor substrateFatty acid oxidationinguinal white adipose tissueInterscapular brown adipose tissueBrowningtriacylglycerolTAG یا triacylglycerols glucose tolerance testRaptorhigh-fat dietphosphoinositide 3-kinaseLipoprotein lipaseMitochondriaRespiratory exchange ratioCCAAT/enhancer-binding proteinSterol regulatory element-binding proteinUncoupling proteinregulatory-associated protein of mTORadiposityDEPTORperoxisome proliferator-activated receptorestrogen-related receptor
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Juliana Magdalon, Patricia Chimin, Thiago Belchior, Rodrigo X. Neves, Marcel A. Vieira-Lara, Maynara L. Andrade, Talita S. Farias, Andressa Bolsoni-Lopes, Vivian A. Paschoal, Alex S. Yamashita, Alicia J. Kowaltowski, William T. Festuccia,