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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 10
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: Journal of Lipid Research; v. 53, n. 6, p. 1117-1125, JUN 2012.
Web of Science Citations: 56
Abstract

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)

FAPESP's process: 10/10909-8 - Role of adipose tissue in the development of obesity and associated co-morbidities: investigation of molecular mechanism and search for alternative therapies
Grantee:William Tadeu Lara Festuccia
Support Opportunities: Scholarships in Brazil - Young Researchers
FAPESP's process: 09/15354-7 - Role of adipose tissue in the development of obesity and associated co-morbidities: investigation of molecular mechanism and search for alternative therapies
Grantee:William Tadeu Lara Festuccia
Support Opportunities: Research Grants - Young Investigators Grants