title: Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome.
abstract: In this study, we defined the role of peroxisome proliferator-activated receptor beta/delta (PPARdelta) in metabolic homeostasis by using subtype selective agonists. Analysis of rat L6 myotubes treated with the PPARdelta subtype-selective agonist, GW501516, by the Affymetrix oligonucleotide microarrays revealed that PPARdelta controls fatty acid oxidation by regulating genes involved in fatty acid transport, beta-oxidation, and mitochondrial respiration. Similar PPARdelta-mediated gene activation was observed in the skeletal muscle of GW501516-treated mice. Accordingly, GW501516 treatment induced fatty acid beta-oxidation in L6 myotubes as well as in mouse skeletal muscles. Administration of GW501516 to mice fed a high-fat diet ameliorated diet-induced obesity and insulin resistance, an effect accompanied by enhanced metabolic rate and fatty acid beta-oxidation, proliferation of mitochondria, and a marked reduction of lipid droplets in skeletal muscles. Despite a modest body weight change relative to vehicle-treated mice, GW501516 treatment also markedly improved diabetes as revealed by the decrease in plasma glucose and blood insulin levels in genetically obese ob/ob mice. These data suggest that PPARdelta is pivotal to control the program for fatty acid oxidation in the skeletal muscle, thereby ameliorating obesity and insulin resistance through its activation in obese animals.
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Tanaka
authors.forename: Joji
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iwasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asaba
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hamura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kenta
authors.initials: K
authors.lastname: Magoori
authors.forename: Ryoichi X
authors.initials: RX
authors.lastname: Ioka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tachibana
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Sumi
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Iguchi
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Takefumi
authors.initials: T
authors.lastname: Doi
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Juro
authors.initials: J
authors.lastname: Sakai
mesh_terms: D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004798:Enzymes / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D008099:Liver / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists* / Q000187:drug effects
chemical_list: D004798:Enzymes; D005230:Fatty Acids, Nonesterified; C425931:GW 501516; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D014157:Transcription Factors; D004121:Dimethyl Sulfoxide