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Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes.


ABSTRACT: Peroxisome proliferator-activated receptor-? (PPAR?) is a dietary lipid sensor, whose activation results in hypolipidemic effects. In this study, we investigated whether PPAR? activation affects energy metabolism in white adipose tissue (WAT). Activation of PPAR? by its agonist (bezafibrate) markedly reduced adiposity in KK mice fed a high-fat diet. In 3T3-L1 adipocytes, addition of GW7647, a highly specific PPAR? agonist, during adipocyte differentiation enhanced glycerol-3-phosphate dehydrogenase activity, insulin-stimulated glucose uptake, and adipogenic gene expression. However, triglyceride accumulation was not increased by PPAR? activation. PPAR? activation induced expression of target genes involved in FA oxidation and stimulated FA oxidation. In WAT of KK mice treated with bezafibrate, both adipogenic and FA oxidation-related genes were significantly upregulated. These changes in mRNA expression were not observed in PPAR?-deficient mice. Bezafibrate treatment enhanced FA oxidation in isolated adipocytes, suppressing adipocyte hypertrophy. Chromatin immunoprecipitation (ChIP) assay revealed that PPAR? was recruited to promoter regions of both adipogenic and FA oxidation-related genes in the presence of GW7647 in 3T3-L1 adipocytes. These findings indicate that the activation of PPAR? affects energy metabolism in adipocytes, and PPAR? activation in WAT may contribute to the clinical effects of fibrate drugs.

SUBMITTER: Goto T 

PROVIDER: S-EPMC3073464 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes.

Goto Tsuyoshi T   Lee Joo-Young JY   Teraminami Aki A   Kim Yong-Il YI   Hirai Shizuka S   Uemura Taku T   Inoue Hiroyasu H   Takahashi Nobuyuki N   Takahashi Nobuyuki N   Kawada Teruo T  

Journal of lipid research 20110214 5


Peroxisome proliferator-activated receptor-α (PPARα) is a dietary lipid sensor, whose activation results in hypolipidemic effects. In this study, we investigated whether PPARα activation affects energy metabolism in white adipose tissue (WAT). Activation of PPARα by its agonist (bezafibrate) markedly reduced adiposity in KK mice fed a high-fat diet. In 3T3-L1 adipocytes, addition of GW7647, a highly specific PPARα agonist, during adipocyte differentiation enhanced glycerol-3-phosphate dehydrogen  ...[more]

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