| Project/Area Number |
15K16219
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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 |
Eating habits
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| Research Institution | Tokyo University of Agriculture |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 非アルコール性脂肪性肝炎 / 脂質代謝 / 転写因子 / NASH / SREBP-1 / RNA-Seq / 脂肪肝 / 炎症 |
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| Outline of Final Research Achievements |
We examined the relationship between SREBP-1 and NASH onset / progress, and diet therapy for NASH pathogenesis via SREBP-1. Atherogenic high fat diet was fed to WT and SREBP-1 KO mice to induce NASH. mRNA expression involved in inflammation decreased in SREBP-1 KO mice compared to WT mice. We identified gene X as novel target gene of SREBP-1. In addition, both EPA and DHA which inhibited activation of SREBP-1 ameliorated NASH symptom. Intriguingly, EPA had a greater hepatic triacylglycerol (TG)-reducing effect than DHA. In contrast, DHA had a greater suppressive effect than EPA on hepatic inflammation. These results revealed that both EPA and DHA are effective to treat AHF-induced NASH in mice, but they exert different effects, which indicate that EPA and DHA may be differentially used in the NASH treatment, depending upon the disease’s stage.
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| Academic Significance and Societal Importance of the Research Achievements |
SREBP-1 は、食事による影響を直接的に大きく受けるため、肝臓に対する SREBP-1 の病態生理的役割を明らかにし、エネルギー代謝及び炎症調節の分子メカニズムの解明とそれを制御する新規因子・遺伝子を解明することは、生活習慣病の病態理解を深めるだけでなく、食事パターンや食事の種類といった栄養学的な介入に大きなインパクトを与える可能性を秘め、社会的意義は大きい。
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