2021 Fiscal Year Final Research Report
Study on the mechanisms by which the translation initiation regulating factors induces lipid accumulation in rat liver under protein deprivation.
| Project/Area Number |
19K05916
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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 38050:Food sciences-related
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| Research Institution | Utsunomiya University (2021)
Ochanomizu University (2020)
Nippon Medical School (2019) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | タンパク質 / 翻訳 / 4E-BP1 / eIF4G / 肝臓 / 中性脂肪 |
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| Outline of Final Research Achievements |
Dietary protein deprivation has been shown to induce fatty liver in animals including human. However, the molecular mechanisms underlying such induction are largely unknown. Our previous studies have elucidated that low-protein diet increases eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), which induces hepatic lipid accumulation in rats. In addition, we found that low-protein diet also increased eukaryotic translation initiation factor 4G (eIF4G) in the liver, which could be involved in the regulation of lipid metabolism in the liver. In this study, we examined how 4E-BP1 and eIF4G contributes to hepatic lipid accumulation under protein deprivation. Our results indicated that the 4E-BP1 and eIF4G could regulate lipid metabolism in a different manner. Further studies are necessary to determine the details of these mechanisms.
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| Free Research Field |
栄養生化学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、タンパク質の摂取不足に応答して、翻訳開始因子eIF4Gが、翻訳抑制因子4E-BP1とは異なる機構で脂質代謝調節に関与することを明らかにした。したがって、4E-BP1やeIF4Gは、タンパク質摂取不足による体内のアミノ酸利用の低下と肝脂肪蓄積を結ぶ重要な因子であると考えられた。本研究をさらに発展させて、これらの翻訳開始調節因子の標的因子を同定し、それによって調節される脂質代謝経路を明らかにすることができれば、脂肪肝治療のための新規薬剤の開発が可能となると考えている。また、過栄養による脂肪肝発症メカニズムとの差異もわかれば、発症要因に特化した食事療法の提案も可能となると考えている。
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