title: Sirt1 and Sirt6 mediate beneficial effects of rosiglitazone on hepatic lipid accumulation.
abstract: BACKGROUND
  Sirtuin (Sirt), a sensor of the cell metabolic state, regulates glucose and lipid metabolism. The aim of this study was to address whether rosiglitazone (RGZ) alters hepatic Sirt1 and whether Sirt1 and/or Sirt6 have a regulatory role in the protective effects of RGZ on hepatocyte steatosis.
  
  
  METHODS
  To investigate the effect of RGZ on hepatic Sirt1, rats were administered with RGZ for 6 weeks. The involvement of Sirt1/6 in the RGZ-mediated effect against hepatic steatosis was evaluated by single or double knockdown of Sirt1 and Sirt6 in a hepatocyte steatosis model.
  
  
  RESULTS
  RGZ in vivo increased Sirt1 expression and its activity in rat livers. In a hepatocyte steatosis model, RGZ significantly reduced lipid accumulation and activated the Sirt1/6-LKB1-AMPK pathway. Sirt1 knockdown abolished the effects of RGZ with regard to hepatocyte fat accumulation and the Sirt1/6-LKB1-AMPK pathway, suggesting that Sirt1 is a key regulator of RGZ-mediated metabolic processes. Sirt6 knockdown inhibited the protective effects of RGZ to a lesser extent than Sirt1, and double knockdown of Sirt1/6 showed no synergistic effects.
  
  
  CONCLUSIONS
  Our results demonstrate that Sirt1/6 are involved in the RGZ-mediated effects on hepatocyte steatosis, and the regulatory effects of Sirt1 and Sirt6 are not synergistic but compensatory for improving hepatocyte steatosis.
authors.affiliation: Department of Food and Nutrition and Human Ecology Research Institute, Chonnam National University, Gwangju, Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Diabetes Research Institute, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea.
authors.forename: Jung Mook
authors.initials: JM
authors.lastname: Choi
authors.affiliation: Diabetes Research Institute, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea.
authors.forename: Eugene
authors.initials: E
authors.lastname: Chang
authors.affiliation: Department of Endocrinology and Metabolism, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea.
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Diabetes Research Institute, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea; Department of Endocrinology and Metabolism, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea.
authors.forename: Cheol-Young
authors.initials: CY
authors.lastname: Park
mesh_terms: D000818:Animals; D002460:Cell Line; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D056564:Sirtuin 1; D037761:Sirtuins; C560607:sirtuin 6, rat