- 作者：Hajime Ishii ; Yasuo Horie ; Shigetoshi Ohshima ; Yumiko Anezaki ; Nobukatsu Kinoshita ; Takahiro Dohmen ; Ei Kataoka ; Wataru Sato ; Takashi Goto ; Junko Sasaki ; Takehiko Sasaki ; Sumio Watanabe ; Akira Suzuki
- 关键词：Omega-3 fatty acids ; NASH ; Hepatocellular carcinoma ; Pten ; Reactive oxygen species
- 刊名：Journal of Hepatology
- 出版年：2009
- 出版时间：March 2009
- 年：2009
- 卷：50
- 期：3
- 页码：562-571
- 全文大小：1397 K
Background/Aims
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 AMPKα1-mediated SREBP-1c and increased PPARα 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.