2018 Fiscal Year Final Research Report
The study for the pathogenesis of NASH using three kinds of PNPLA3 gene-modified mice
| Project/Area Number |
16K19351
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Kochi University |
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Principal Investigator |
OCHI Tsunehiro 高知大学, 教育研究部医療学系基礎医学部門, 助教 (30617840)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | NASH / PNPLA3 / PNPLA3 mutation / XBP-1 |
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| Outline of Final Research Achievements |
A sequence variation (I148M) in the patatin-like phospholipase domain-containing protein 3/adiponutrin(PNPLA3) gene and Endoplasmic reticulum (ER) stress have been reported to be important pathological characteristics in NAFLD/NASH. To clarify, therefore, the pathogenesis of NAFLD/NASH, we established three kinds of PNPLA3 gene-modified mice and investigated the phenotypes and involved factors under ER stress and other conditions. Our observations would indicate that PNPLA3 has an important role in hepatic fatty acid and triglyceride metabolism through XBP1 under ER stress. Moreover, human PNPLA3I148M knockin mice had a tendency to develop hepatic steatosis with high fat diet. Taken together, PNPLA3 and ER stress are important for the pathogenesis of NAFLD/NASH.
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| Free Research Field |
非アルコール性脂肪性肝疾患（NAFLD）、非アルコール性脂肪肝炎（NASH）、糖代謝
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| Academic Significance and Societal Importance of the Research Achievements |
近年、メタボリックシンドロームとされる肥満、糖尿病、高血圧、脂質異常症は増加の一途であり、わが国でも社会問題となっている。それと並行して、メタボリックシンドロームを原因とした脂肪肝とそれに伴う慢性肝疾患（NAFLD/NASH）も増加してきている。
PNPLA3遺伝子多型およびERストレスが関与しているNAFLD/NASH発症メカニズムを解明することは、今まで推奨されてきた食事療法・運動療法などの治療に加えて、患者の病態に合わせたオーダーメイド治療や新たな創薬へ繋がることが期待され、学術的・社会的意義は高いものと思われる。
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