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ID 53995
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Author
Matsuyama, Makoto
Yamaguchi, Satoshi
Katayama, Akihiro
Wada, Nozomu
Yasunaka, Tetsuya
Takaki, Akinobu Kakenhi
Watanabe, Eijiro
Abstract
 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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Published Date
2016-02-17
Publication Title
Scientific Reports
Volume
volume6
Publisher
Nature Publishing Group
Start Page
21721
ISSN
2045-2322
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1038/srep21721
Related Url
http://www.okayama-u.ac.jp/tp/release/release_id367.html
language
英語
Copyright Holders
© 2016 Nature Publishing Group
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Refereed
True
DOI
PubMed ID