2023 Fiscal Year Final Research Report
Investigation of the anti-atherosclerosis and NASH effects of a newly identified myokine
| Project/Area Number |
21K07395
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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 52010:General internal medicine-related
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
竹本 稔 国際医療福祉大学, 医学部, 主任教授 (60447307)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | マイオカイン / NASH / NAFLD |
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| Outline of Final Research Achievements |
In this study, we investigated the role of R3hdml, a skeletal muscle-derived secretory factor, in NAFLD. Using R3hdml knockout mice, we found that R3hdml deficiency exacerbates steatosis. The mechanism is suggested to be that R3hdml promotes PIP3-mediated AKT signaling and suppresses MET-mediated PTK2 signaling. Furthermore, we found a positive correlation between serum R3hdml antibody levels and the Fib-4 index, a marker of liver fibrosis. In addition, antibody screening identified PEPCK antibody as a NASH-related factor. In diabetic patients, PEPCK antibody levels were also found to be associated with prognosis.
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| Free Research Field |
糖尿病・代謝
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| Academic Significance and Societal Importance of the Research Achievements |
生活習慣の欧米化に伴い、虚血性心疾患などの動脈硬化性疾患の罹患率は増え続けており、常に我が国の死因の上位を占めている。動脈硬化は血管壁における慢性炎症に伴い、脂質の異常蓄積によって生じる。さらに脂質の肝臓への蓄積する病態に、非アルコール性脂肪肝があり、時に炎症（非アルコール性脂肪性肝炎（NASH））が慢性化し、肝硬変、肝がんを生じる。脂肪肝からNASHまでを含む一連の肝疾患（NAFLD）の罹患者は1,000万人以上であると推定されており、動脈硬化とともに、その予防法や治療法の開発は喫緊の課題である。R3hdmlとNASHとの関連を明らかにすることで、新たな治療戦略開発につながる可能性がある。
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