論文 - 詳細
| RRC ID | 39291 |
|---|---|
| 著者 | Nakatsuka A, Matsuyama M, Yamaguchi S, Katayama A, Eguchi J, Murakami K, Teshigawara S, Ogawa D, Wada N, Yasunaka T, Ikeda F, Takaki A, Watanabe E, Wada J. |
| タイトル | Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis. |
| ジャーナル | Sci Rep |
| 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. |
| 巻・号 | 6 |
| ページ | 21721 |
| 公開日 | 2016-2-17 |
| DOI | 10.1038/srep21721 |
| PII | srep21721 |
| PMID | 26883167 |
| PMC | PMC4756298 |
| MeSH | Animals Apoptosis Cells, Cultured Clathrin Heavy Chains / metabolism Diet, High-Fat Disease Models, Animal Down-Regulation Gene Knockdown Techniques Genetic Predisposition to Disease Hepatocytes / cytology* Humans Mice Non-alcoholic Fatty Liver Disease / enzymology Non-alcoholic Fatty Liver Disease / genetics Non-alcoholic Fatty Liver Disease / pathology* Obesity / prevention & control Phosphatidylethanolamine N-Methyltransferase / genetics* Phosphatidylethanolamine N-Methyltransferase / metabolism* Tumor Suppressor Protein p53 / metabolism |
| IF | 3.998 |
| 引用数 | 10 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | p3xFLAG-CMV-10-Pemt (RDB14190) pcDNA3-myc-CHC(232-340) (RDB14191) pcDNA3-myc-CHC(1074-1406) (RDB14192) pcDNA3-myc-CHC(1267-1513) (RDB14193) pcDNA3-myc-CHC(1-1676) (RDB14194) pcDNA3.1-p53-HA (RDB14195) pcDNA3.1-FLAG-Pemt-HA (RDB14196). |