rlip76, a glutathione-conjugate transporter, plays a major role in the pathogenesis of metabolic syndromerlip76 glutathione-conjugate运输车,在代谢综合征的发病机理中起着重要作用.pdfVIP

RLIP76, a Glutathione-Conjugate Transporter, Plays a Major Role in the Pathogenesis of Metabolic Syndrome 1 1 2 1 1 Jyotsana Singhal , Lokesh Nagaprashantha , Rit Vatsyayan , Sanjay Awasthi , Sharad S. Singhal * 1 Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, National Medical Center, Duarte, California, United States of America, 2 Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas, United States of America Abstract Purpose: Characteristic hypoglycemia, hypotriglyceridemia, hypocholesterolemia, lower body mass, and fat as well as pronounced insulin-sensitivity of RLIP762/ 2 mice suggested to us the possibility that elevation of RLIP76 in response to stress could itself elicit metabolic syndrome (MSy). Indeed, if it were required for MSy, drugs used to treat MSy should have no effect on RLIP762/ 2 mice. Research Design and Methods: Blood glucose (BG) and lipid measurements were performed in RLIP76+/+ and RLIP762/ 2 mice, using Ascensia Elite GlucometerH for glucose and ID Labs kits for cholesterol and triglycerides assays. The ultimate effectors of gluconeogenesis are the three enzymes: PEPCK, F-1,6-BPase, and G6Pase, and their expression is regulated by PPARc and AMPK. The activity of these enzymes was tested by protocols standardized by us. Expressions of RLIP76, PPARa, PPARc, HMGCR, pJNK, pAkt, and AMPK were performed by Western-blot and tissue staining. Results: The concomitant activation of AMPK and PPARc by inhibiting transport activity of RLIP76, despite inhibited activity of key glucocorticoid-regulated hepatic gluconeogenic enzymes like PEPCK, G6Pase and F-1,6-BP in RLIP762/ 2 mice,