cross regulation of sirtuin 1, ampk, and pparγ in conjugated linoleic acid treated adipocytes交叉监管sirtuin蛋白1,ampk,pparγ共轭亚油酸对脂肪细胞.pdfVIP

Cross Regulation of Sirtuin 1, AMPK, and PPARc in Conjugated Linoleic Acid Treated Adipocytes 1 2 2 3 Shan Jiang , Wei Wang , Jess Miner , Michael Fromm * 1 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America, 2 Department of Animal Science, University of Nebraska, Lincoln, Nebraska, United States of America, 3 Center for Biotechnology, University of Nebraska, Lincoln, Nebraska, United States of America Abstract Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride (TG) levels in adipocytes through multiple pathways, with AMP-activated protein kinase (AMPK) generally facilitating, and peroxisome proliferator-activated receptor c (PPARc) generally opposing these reductions. Sirtuin 1 (SIRT1), a histone/protein deacetylase that affects energy homeostasis, often functions coordinately with AMPK, and is capable of binding to PPARc, thereby inhibiting its activity. This study investigated the role of SIRT1 in the response of 3T3-L1 adipocytes to t10c12 CLA by testing the following hypotheses: 1) SIRT1 is functionally required for robust TG reduction; and 2) SIRT1, AMPK, and PPARc cross regulate each other. These experiments were performed by using activators, inhibitors, or siRNA knockdowns that affected these pathways in t10c12 CLA-treated 3T3-L1 adipocytes. Inhibition of SIRT1 amounts or activity using siRNA, sirtinol, nicotinamide, or etomoxir attenuated the amount of TG loss, while SIRT1 activator SRT1720 increased the TG loss. SRT1720 increased AMPK activity while sirtuin-specific inhibitors decreased AMPK activity. Reciprocally, an AMPK inhibitor reduced