Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis

Atsuko Nakatsuka, Makoto Matsuyama, Satoshi Yamaguchi, Akihiro Katayama, Jun Eguchi, Kazutoshi Murakami, Sanae Teshigawara, Daisuke Ogawa, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Eijiro Watanabe, Jun Wada

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number21721
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Feb 17 2016

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Phosphatidylethanolamine N-Methyltransferase
Fatty Liver
High Fat Diet
Sucrose
Hepatocyte Nuclear Factor 4
Clathrin Heavy Chains
Obesity
F-Box Proteins
Messenger RNA
Liver
Cyclin D1
Hepatocytes
Body Mass Index
Apoptosis
Diet

ASJC Scopus subject areas

  • General

Cite this

Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis. / Nakatsuka, Atsuko; Matsuyama, Makoto; Yamaguchi, Satoshi; Katayama, Akihiro; Eguchi, Jun; Murakami, Kazutoshi; Teshigawara, Sanae; Ogawa, Daisuke; Wada, Nozomu; Yasunaka, Tetsuya; Ikeda, Fusao; Takaki, Akinobu; Watanabe, Eijiro; Wada, Jun.

In: Scientific Reports, Vol. 6, 21721, 17.02.2016.

Research output: Contribution to journalArticle

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AU - Matsuyama, Makoto

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AU - Eguchi, Jun

AU - Murakami, Kazutoshi

AU - Teshigawara, Sanae

AU - Ogawa, Daisuke

AU - Wada, Nozomu

AU - Yasunaka, Tetsuya

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AU - Takaki, Akinobu

AU - Watanabe, Eijiro

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