Major involvement of mTOR in the PPAR gamma-induced stimulation of adipose tissue lipid uptake and fat accretion

Autor(es)

Blanchard, Pierre-Gilles ^[1] ; Festuccia, William T. ^[2] ; Houde, Vanessa P. ^[1] ; St-Pierre, Philippe ^[1] ; Brule, Sophie ^[1] ; Turcotte, Veronique ^[1] ; Cote, Marie ^[1] ; Bellmann, Kerstin ^[1] ; Marette, Andre ^[1] ; Deshaies, Yves ^[1]

Afiliação do(s) autor(es)

^[1] Univ Laval, Quebec Heart & Lung Inst, Fac Med, Dept Med, Ste Foy, PQ G1V 4G5 - Canada

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Lipid Research; v. 53, n. 6, p. 1117-1125, JUN 2012.
• Citações Web of Science: 56

Resumo

Evidence points to a role of the mammalian target of rapamycin (mTOR) signaling pathway as a regulator of adiposity, yet its involvement as a mediator of the positive actions of peroxisome proliferator-activated receptor (PPAR)gamma agonism on lipemia, fat accretion, lipid uptake, and its major determinant lipoprotein lipase (LPL) remains to be elucidated. Herein we evaluated the plasma lipid profile, triacylglycerol (TAG) secretion rates, and adipose tissue LPL-dependent lipid uptake, LPL expression/activity, and expression profile of other lipid metabolism genes in rats treated with the PPAR gamma agonist rosiglitazone (15 mg/kg/day) in combination or not with the mTOR inhibitor rapamycin (2 mg/kg/day) for 15 days. Rosiglitazone stimulated adipose tissue mTOR complex 1 and AMPK and induced TAG-derived lipid uptake (136%), LPL mRNA/activity (2- to 6-fold), and fat accretion in subcutaneous (but not visceral) white adipose tissue (WAT; 50%) and in brown adipose tissue (BAT; 266%). Chronic mTOR inhibition attenuated the upregulation of lipid uptake, LPL expression/activity, and fat accretion induced by PPAR gamma activation in both subcutaneous WAT and BAT, which resulted in hyperlipidemia. In contrast, rapamycin did not affect most of the other WAT lipogenic genes upregulated by rosiglitazone. Together these findings demonstrate that mTOR is a major regulator of adipose tissue LPL-mediated lipid uptake and a critical mediator of the hypolipidemic and lipogenic actions of PPAR gamma activation.-Blanchard, P-G., W. T. Festuccia, V. P. Houde, P. St-Pierre, S. Brule, V. Turcotte, M. Cote, K. Bellmann, A. Marette, and Y. Deshaies. Major involvement of mTOR in the PPAR gamma-induced stimulation of adipose tissue lipid uptake and fat accretion. J. Lipid Res. 2012. 53: 1117-1125. (AU)

• Processo FAPESP: 10/10909-8 - Envolvimento do tecido adiposo no desenvolvimento da obesidade e patologias associadas: investigação dos mecanismos moleculares e busca de novas alternativas terapêuticas
• Beneficiário: William Tadeu Lara Festuccia
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 09/15354-7 - Envolvimento do tecido adiposo no desenvolvimento da obesidade e patologias associadas: investigação dos mecanismos moleculares e busca de novas alternativas terapêuticas
• Beneficiário: William Tadeu Lara Festuccia
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores