title: Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in hepatocyte-specific Pten-deficient mice.
abstract: OBJECTIVE
  Eicosapentaenoic acid (EPA) has been known as a reagent for improving lipid metabolism and inflammation. Hepatocyte-specific Pten-deficient mice exhibit hepatic lesions analogous to non-alcoholic steatohepatitis (NASH). Therefore, we administered EPA to Pten-deficient mice to investigate the mechanisms of NASH.
  
  
  METHODS
  Pten-deficient mice were assigned to a control group fed with a standard chow or an EPA group fed with a 5% EPA-supplemented standard chow. At 40 weeks, livers from each group were processed to measure triglyceride content, gene expression analysis, Western blotting analysis, and histological examination. Level of serum reactive oxygen species (ROS) was also determined. Forty- and 76-week-old mice were used in tumor burden experiments.
  
  
  RESULTS
  EPA-ameliorated hepatic steatosis in Pten-deficient mice was based on decreased expression of AMPKalpha1-mediated SREBP-1c and increased PPARalpha expression. The EPA group exhibited less severe chronic hepatic inflammation compared to the control group, resulting from decreased ROS formation and a dramatically low ratio of arachidonic acid to EPA. Moreover, EPA inhibited development of hepatocellular carcinoma (HCC) in Pten-deficient mice based on an inhibition of MAPK activity and a low ratio of oleic to stealic acid, and a reduction in ROS formation.
  
  
  CONCLUSIONS
  EPA ameliorated steatohepatitis and development of HCC in Pten-deficient mice.
authors.affiliation: Department of Gastroenterology, Akita University School of Medicine, Akita, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Ishii
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Horie
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Ohshima
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Anezaki
authors.forename: Nobukatsu
authors.initials: N
authors.lastname: Kinoshita
authors.forename: Takahiro
authors.initials: T
authors.lastname: Dohmen
authors.forename: Ei
authors.initials: E
authors.lastname: Kataoka
authors.forename: Wataru
authors.initials: W
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Goto
authors.forename: Junko
authors.initials: J
authors.lastname: Sasaki
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Hirohide
authors.initials: H
authors.lastname: Ohnishi
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000172:deficiency*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D015118:Eicosapentaenoic Acid; D020928:Mitogen-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse