2018 Fiscal Year Final Research Report
New development of animal model of non-obese nonalcoholic steatohepatitis and its corrective establishment
| Project/Area Number |
16K00852
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Eating habits
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 非アルコール性脂肪性肝炎（NASH） / 脂肪肝 / 肥満症 / ミフェプリストン / グルココルチコイド / 肝星状細胞 / 肝非実質細胞 |
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| Outline of Final Research Achievements |
Mifepristone, a putative steroid receptor antagonist, clinically serves as an anti-cancer agent. However, the metabolic effects of long-term treatment with mifepristone remain largely unclear. This study aimed to determine whether mifepristone influences glucose metabolism and hepatic steatosis in healthy mice fed with regular diet (RD). The 12-week administration of mifepristone as a mixture with RD markedly increased a percentage of liver wet weight, the level of fasting blood glucose, the amount of food consumption and a percentage of body fat, in a dose-dependent manner ranging from 0.1 to 30 mg/kg/day. Bodipy 493/503 staining of liver specimens revealed the development of hepatic steatosis. Moreover, it increased in the expression of both gene and protein which have a regulation on glucose metabolism in a liver of the mifepristone fed mouse. These results suggest that long term administration of mifepristone leads to the development of non-obese non-alcoholic fatty liver disease.
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| Free Research Field |
生理学
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| Academic Significance and Societal Importance of the Research Achievements |
肥満が危険因子の一つである非アルコール性脂肪性肝炎（NASH: Nonalcoholic steatohepatitis）の患者数は、肥満の程度が比較的軽い日本において増加している。この発症メカニズムを解明するための最適な非肥満非アルコール性脂肪肝モデル動物の開発を行った。
従来、非肥満NASHモデル動物には、高コレステロール食事誘発性モデルの報告はあるが、通常食を使用したモデル動物の報告はない。本研究において、通常食と小分子化合物を用いた新しい非肥満非アルコール性脂肪肝モデル動物を確立することができ、非肥満者におけるNASHの病態解明、新規治療標的の探索および薬効評価に有用であると考えられる。
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