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ID 53141
フルテキストURL
著者
Ishikawa, Hisashi Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Takaki, Akinobu Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci 科研費研究者番号
Tsuzaki, Ryuichiro Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Yasunaka, Tetsuya Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Koike, Kazuko Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Shimomura, Yasuyuki Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Seki, Hiroyuki Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Matsushita, Hiroshi Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Miyake, Yasuhiro Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Ikeda, Fusao Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Shiraha, Hidenori Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Nouso, Kazuhiro Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Yamamoto, Kazuhide Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
抄録
Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC). Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid), an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1) high-fat diet (HFD) (control group); 2) HFD mixed with 0.28% L-carnitine (L-carnitine group); and 3) HFD mixed with 0.01% alpha-tocopherol (alpha-tocopherol group). After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial beta-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although alpha-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by upregulating the mitochondrial beta-oxidation and redox system.
発行日
2014-07-01
出版物タイトル
PLoS ONE
9巻
7号
出版者
Public Library Science
ISSN
1932-6203
資料タイプ
学術雑誌論文
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/53133
言語
English
著作権者
© 2014 Ishikawa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
論文のバージョン
publisher
査読
有り
DOI
Web of Sience KeyUT