ID | 53995 |
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Nakatsuka, Atsuko
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Matsuyama, Makoto
Shigei Medical Research Institute
Yamaguchi, Satoshi
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Katayama, Akihiro
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Eguchi, Jun
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Murakami, Kazutoshi
Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Teshigawara, Sanae
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Ogawa, Daisuke
Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Wada, Nozomu
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yasunaka, Tetsuya
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ikeda, Fusao
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Takaki, Akinobu
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Watanabe, Eijiro
Dainippon Sumitomo Pharma
Wada, Jun
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | Although obesity is undoubtedly major risk for non-alcoholic steatohepatitis (NASH), the presence of lean NASH patients with normal body mass index has been recognized. Here, we report that the insufficiency of phosphatidylethanolamine N-methyltransferase (PEMT) is a risk for the lean NASH. The Pemt−/− mice fed high fat-high sucrose (HFHS) diet were protected from diet-induced obesity and diabetes, while they demonstrated prominent steatohepatitis and developed multiple liver tumors. Pemt exerted inhibitory effects on p53-driven transcription by forming the complex with clathrin heavy chain and p53, and Pemt−/− mice fed HFHS diet demonstrated prominent apoptosis of hepatocytes. Furthermore, hypermethylation and suppressed mRNA expression of F-box protein 31 and hepatocyte nuclear factor 4α resulted in the prominent activation of cyclin D1. PEMT mRNA expression in liver tissues of NASH patients was significantly lower than those with simple steatosis and we postulated the distinct clinical entity of lean NASH with insufficiency of PEMT activities.
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備考 | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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発行日 | 2016-02-17
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出版物タイトル |
Scientific Reports
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巻 | 6巻
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出版者 | Nature Publishing Group
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開始ページ | 21721
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ISSN | 2045-2322
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資料タイプ |
学術雑誌論文
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オフィシャル URL | http://dx.doi.org/10.1038/srep21721
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関連URL | http://www.okayama-u.ac.jp/tp/release/release_id367.html
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言語 |
英語
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著作権者 | © 2016 Nature Publishing Group
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論文のバージョン | publisher
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査読 |
有り
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DOI | |
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