2022 Fiscal Year Final Research Report
Molecular mechanism of oxysterol 7-alpha hydroxylase on NASH progression
| Project/Area Number |
19K15764
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 38050:Food sciences-related
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| Research Institution | Showa University (2021-2022)
The University of Tokyo (2019-2020) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | NASH / 酸化ステロール代謝 / 胆汁酸合成経路 / CYP7B1 |
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| Outline of Final Research Achievements |
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide affecting more than 25% of adult population. Whereas NAFLD encompasses from benign simple steatosis to non-alcoholic steatohepatitis (NASH), detail of its transition mechanisms underlying the pathogenesis of that are still unknown. In this study, we focused on the hepatic Cyp7b1 gene, whose expression was downregulated in the liver of ob/ob mice and MCD diet-fed mice based on previous microarray data. We investigated the effect of CYP7B1 recovery on the phenotype of NASH under conditions of NASH development and its association with general NASH features such as oxidative and lipid stress. We found that CYP7B1 recovery suppressed hepatitis and fibrosis. We also found that the induction of lipid stress and oxidative stress seen early in the development of NASH suppresses Cyp7b1 transcription in hepatocytes.
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| Free Research Field |
分子細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
食習慣の欧米化による肥満に起因する糖尿病や循環器疾患、非アルコール性脂肪肝(NAFLD)などの生活習慣病の罹患者増加は医療費増大に直結し、我が国においても大きな問題となっている。なかでも、NAFLDを罹患する人口は年々増加しており、非アルコール性脂肪肝炎（NASH）へと進展した潜在患者は100~200万人いるとされている。
本研究では、NASHの炎症や線維化に関わると思われる因子を同定し、その発現回復がNASH進行を緩和させることを見出した。加えて、NASH進行時の当該因子の発現低下メカニズムを明らかにした。
これらの成果はNASH進行を予防する機能性食品の創製に繋がることが期待される。
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