title: Inhibition of uncoupling protein 2 with genipin exacerbates palmitate-induced hepatic steatosis.
abstract: BACKGROUND
  Uncoupling protein 2 (UCP2) was reported to be involved in lipid metabolism through regulating the production of superoxide anion. However, the role of UCP2 in hepatocytes steatosis has not been determined. We hypothesized that UCP2 might regulate hepatic steatosis via suppressing oxidative stress.
  
  
  RESULTS
  We tested this hypothesis in an in vitro model of hepatocytic steatosis in HepG2 cell lines induced by palmitic acid (PA). We found that treatment with PA induced an obvious lipid accumulation in HepG2 cells and a significant increase in intracellular triglyceride content. Moreover, the specific inhibition of UCP2 by genipin remarkably exacerbated PA-induced hepatocytes steatosis. Interestingly, the PA-induced superoxide overproduction can also be enhanced by incubation with genipin. In addition, administration with the antioxidant tempol abolished genipin-induced increase in intracellular lipid deposition. We further found that genipin significantly increased the protein expression of fatty acid translocase (FAT)/CD36.
  
  
  CONCLUSIONS
  These findings suggest that UCP2 plays a protective role in PA-induced hepatocytic steatosis through ameliorating oxidative stress.
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, 270 Rongdu Rd, Tianhui Town, Jinniu District, Chengdu 610083, Sichuan Province, People's Republic of China.
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.forename: De
authors.initials: D
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.forename: Bing
authors.initials: B
authors.lastname: Tang
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yang
mesh_terms: D018955:CD36 Antigens / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D039823:Iridoids / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D019308:Palmitic Acid / Q000633:toxicity*; D014280:Triglycerides / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D018955:CD36 Antigens; D007473:Ion Channels; D039823:Iridoids; D024101:Mitochondrial Proteins; D014280:Triglycerides; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D019308:Palmitic Acid; C007834:genipin