rosiglitazone-induced mitochondrial biogenesis in white adipose tissue is independent of peroxisome proliferator-activated receptor γ coactivator-1αrosiglitazone-induced线粒体生物起源在白色脂肪组织是独立于过氧物酶体proliferator-activated受体γcoactivator-1α.pdfVIP

Rosiglitazone-Induced Mitochondrial Biogenesis in White Adipose Tissue Is Independent of Peroxisome Proliferator-Activated Receptor c Coactivator-1a 1 ` 1 1 1 2 1 Rosario Pardo , Natalia Enguix , Jaime Lasheras , Juan E. Feliu , Anastasia Kralli , Josep A. Villena * ` 1 Laboratory of Metabolism and Obesity, Unit of Diabetes and Metabolism, Vall d’Hebron-Institut de Recerca, Universitat Autonoma de Barcelona, Barcelona, Spain, 2 Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, United States of America Abstract Background: Thiazolidinediones, a family of insulin-sensitizing drugs commonly used to treat type 2 diabetes, are thought to exert their effects in part by promoting mitochondrial biogenesis in white adipose tissue through the transcriptional coactivator PGC-1a (Peroxisome Proliferator-Activated Receptor c Coactivator-1a). Methodology/Principal Findings: To assess the role of PGC-1a in the control of rosiglitazone-induced mitochondrial biogenesis, we have generated a mouse model that lacks expression of PGC-1a specifically in adipose tissues (PGC-1a-FAT- KO mice). We found that expression of genes encoding for mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle or fatty acid oxidation, was similar in white adipose tissue of wild type and PGC-1a-FAT-KO mice. Furthermore, the absence of PGC-1a did not prevent the positive effect of rosiglitazone on mitochondrial gene expression or biogenesis, but it precluded the induction by rosiglitazone of UCP1 and other brown fat-spe