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

Abstract

Peroxisome proliferator-activated receptor-α (PPAR α ) is a dietary lipid sensor, whose activation results in hypolipidemic effects. In this study, we investigated whether PPAR α activation affects energy metabolism in white adipose tissue (WAT). Activation of PPAR α by its agonist (bezafi brate) markedly reduced adiposity in KK mice fed a high-fat diet. In 3T3-L1 adipocytes, addition of GW7647, a highly specifi c PPAR α 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 α activation. PPAR α activation induced expression of target genes involved in FA oxidation and stimulated FA oxidation. In WAT of KK mice treated with bezafi brate, both adipogenic and FA oxidation-related genes were signifi cantly upregulated. These changes in mRNA expression were not observed in PPAR α -defi cient mice. Bezafi brate treatment enhanced FA oxidation in isolated adipocytes, suppressing adipocyte hypertrophy. Chromatin immunoprecipitation (ChIP) assay revealed that PPAR α was recruited to promoter regions of both adipogenic and FA oxidation-related genes in the presence of GW7647 in 3T3- L1 adipocytes. These fi ndings indicate that the activation of PPAR α affects energy metabolism in adipocytes, and PPAR α activation in WAT may contribute to the clinical effects of fibrate drugs. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.