A novel mechanism of fatty liver by lipoprotein uptake
| Project/Area Number |
19H02916
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Meiji University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | protein deficiency / IGF-I / FGF21 / VLDL receptor / タンパク質欠乏 / VLDLR / VLDL受容体 / 脂肪肝 |
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| Outline of Research at the Start |
タンパク質欠乏時には成長停止・筋肉量低下などの栄養欠乏症状が現れる一方で、肝臓には異所性脂肪蓄積がみられる。本研究では、「タンパク質欠乏時のFGF21増加がIGF-Iの血中濃度低下を介して筋タンパク質量低下を引き起こし、余剰のエネルギーが生じる。同時に肝臓でVLDL受容体（VLDLR）が高発現し、肝臓にVLDLを取り込むことによって脂肪が蓄積する。」という新しい脂肪肝生成機構を検証する。具体的には、①FGF21合成増加と血中IGF-I濃度の低下で生じる筋肉量の減少が脂肪肝形成を引き起こす、②脂肪肝発症の直接的な要因はVLDLRによるリポタンパク質取り込みである、の２点を明らかにする。
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| Outline of Final Research Achievements |
The purpose of this study was to elucidate a new mechanism by which liver fat increases during protein deficiency. For this purpose, the following hypotheses were tested. “Increase in FGF21 during protein deficiency causes a decrease in muscle mass through a decrease in blood levels of IGF-I, resulting in the generation of excess energy. At the same time, VLDLR is highly expressed in the liver, and fat is accumulated in the liver by uptake of VLDL.” From the results of the research, we were able to clarify a new mechanism that "A decrease in the blood concentration of IGF-I during protein deficiency causes a decrease in muscle weight, and excess energy is taken up in the liver as sugar and accumulated as fat."
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| Academic Significance and Societal Importance of the Research Achievements |
タンパク質欠乏下において、体タンパク質合成の材料であるアミノ酸が不足していてもIGF-Iが存在すれば体タンパク質合成が活性化・維持されることを示した点、および肝臓VLDLR増加が必ずしも脂肪肝を引き起こさないことを示した点で、本研究は学術的意義のある成果を出すことができた。また、本研究で対象とするタンパク質欠乏時の肝臓脂肪増加は、筋肉量低下を伴う高齢者などにおける異所性脂肪蓄積のモデルとなる。異所性脂肪蓄積における筋肉量低下やIGF-I低下の意義を示すことで、その予防に貢献することが期待される。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Essential Amino Acid Intake Is Required for Sustaining Serum Insulin‐Like Growth Factor‐I Levels but Is Not Necessarily Needed for Body Growth2022
Author(s)
Nishi H, Uchida K, Saito M, Yamanaka D, Nagata H, Tomoshige H, Miyata I, Ito K, Toyochima Y, Takahashi S-I, Hakuno F, Takenaka A
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Journal Title
Cells
Volume: 11
Issue: 9
Pages: 1523-1523
DOI
Related Report
Peer Reviewed / Open Access
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