期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：26
页码：15924-15929
DOI：10.1073/pnas.0306981100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In this study, we defined the role of peroxisome proliferator-activated receptor {beta}/{delta} (PPAR{delta}) in metabolic homeostasis by using subtype selective agonists. Analysis of rat L6 myotubes treated with the PPAR{delta} subtype-selective agonist, GW501516 , by the Affymetrix oligonucleotide microarrays revealed that PPAR{delta} controls fatty acid oxidation by regulating genes involved in fatty acid transport, {beta}-oxidation, and mitochondrial respiration. Similar PPAR{delta}-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 PPAR{delta} 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.
