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

Peroxisome proliferator-activated receptor-alpha (PPAR alpha) is a dietary lipid sensor, whose activation results in hypolipidemic effects. In this study, we investigated whether PPAR alpha activation affects energy metabolism in white adipose tissue (WAT). Activation of PPAR alpha by its agonist (beza-fibrate) markedly reduced adiposity in KK mice fed a high-fat diet. In 3T3-L1 adipocytes, addition of GW7647, a highly specific PPAR alpha 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 alpha activation. PPAR alpha 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 alpha-deficient mice. Bezafibrate treatment enhanced FA oxidation in isolated adipocytes, suppressing adipocyte hypertrophy. Chromatin immunoprecipitation (ChIP) assay revealed that PPAR alpha was recruited to promoter regions of both adipogenic and FA oxidation-related genes in the presence of GW7647 in 3T3-L1 adipocytes.(jlr) These findings indicate that the activation of PPAR alpha affects energy metabolism in adipocytes, and PPAR alpha activation in WAT may contribute to the clinical effects of fibrate drugs.-Goto, T., J-Y. Lee, A. Teraminami, Y-I. Kim, S. Hirai, T. Uemura, H. Inoue, N. Takahashi, and T. Kawada. Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes. J. Lipid Res. 2011. 52: 873-884.