title: Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes.
abstract: 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 dehydrogenase activity, insulin-stimulated glucose uptake, and adipogenic gene expression. However, triglyceride accumulation was not increased by PPARα activation. PPARα 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 PPARα-deficient mice. Bezafibrate treatment enhanced FA oxidation in isolated adipocytes, suppressing adipocyte hypertrophy. Chromatin immunoprecipitation (ChIP) assay revealed that PPARα 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 PPARα affects energy metabolism in adipocytes, and PPARα activation in WAT may contribute to the clinical effects of fibrate drugs.
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Aki
authors.initials: A
authors.lastname: Teraminami
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Shizuka
authors.initials: S
authors.lastname: Hirai
authors.forename: Taku
authors.initials: T
authors.lastname: Uemura
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inoue
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004041:Dietary Fats / Q000009:adverse effects; D005227:Fatty Acids / Q000378:metabolism; D015151:Immunoblotting; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D047493:PPAR alpha; D001629:Bezafibrate