| Project/Area Number |
18K10993
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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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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
林 由美 名古屋大学, 医学系研究科(保健), 講師 (30632707)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | NASH / 動脈硬化 / SHRSP5 / 心筋梗塞 / 胆汁酸 / 肝臓X受容体 / 非アルコール性脂肪性肝炎 |
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| Outline of Final Research Achievements |
Liver X receptor (LXR) activity is expected to have an innovative effect of extracting cholesterol from once formed atherosclerotic lesions and regressing arteriosclerosis, but it also induces a lipid synthesis system gene (SREBP1c). It has the drawback of further exacerbating hepatic lipid deposition. In this study, in order to overcome this drawback, the applicants have a special purpose (1): the inhibitory effect of bile acid on SREBP1c activity and the purpose (2): the efficacy of vabagenin, which is a novel ligand candidate for LXR activity that does not activate SREBP1c. As a result of examination using the NASH- myocardial infarction onset model (SHRSP5 / Dmcr rat), the lipid deposition in the arteries was improved without aggravating fatty liver.
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| Academic Significance and Societal Importance of the Research Achievements |
非アルコール性脂肪性肝炎(NASH)は、大きな自覚症状がないことから長年軽視されてきた。しかしながら、NASHが肝硬変、肝がんに移行することが明らかとなったことで、積極的な治療ターゲットという認識に変わってきた。また、NASHは肝臓だけにとどまらず、メタボリックシンドロームを背景とした糖尿病、脂質異常症、高血圧を悪化させ、虚血性心疾患の発症率と死亡率を2倍以上高くすることも、予後を悪くする原因となっている。増大する医療費を削減するため、自覚症状が少ない早期のNASHのうちから、積極的な治療介入を行うことができれば、致死的な虚血性心疾患への進行を事前に食い止めることができる。
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