2023 Fiscal Year Final Research Report
Novel therapeutic strategies for fatty liver improvement (IGF-I effects on hepatocytes).
| Project/Area Number |
21K16342
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 成人成長ホルモン分泌不全症 / 成長ホルモン / IGF-I / 脂肪肝 / ABCA1 / FoxO1 / NAFLD/NASH |
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| Outline of Final Research Achievements |
Adult GH deficiency of secretion (AGHD) can lead to fatty liver to cirrhosis. The efficacy of IGF-I supplementation in this condition is unknown, and the relationship between IGF-I and ABCA1 (closely related to TG synthesis) expression was investigated in the present study, suggesting that ABCA1 expression increases upon IGF-I stimulation in HepG2 and may promote ABCA1 transcriptional activity via PI3-K/Akt/FoxO1. IGF-I treatment of hepatic lipolipidaemia in a GH-secretory-deficient mouse model increased hepatic ABCA1 expression, decreased intracellular lipid accumulation, decreased serum TG and increased HDL In FoxO1 studies, 2-ME2 promoted hepatic ABCA1 expression via the PI3K/Akt/FoxO1 pathway and decreased hepatic lipid content. . The possibility that IGF-I could be an effective therapeutic strategy for fatty liver in AGHD was demonstrated in this study through basic experiments.
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| Free Research Field |
内分泌代謝学分野
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| Academic Significance and Societal Importance of the Research Achievements |
AGHD患者に対するIGF-Iにおける意義や詳細なメカニズムは不明で、AGHDにおける脂肪肝形成のメカニズムにおけるIGF-Iの役割を明らかにし、AGHDで引き起こされる脂肪肝/NAFLD/NASHに対し、IGF-Iを補充することで脂肪肝が改善する機序の一つを解析できた学術的意義は大きい。またAGHDにおける脂肪肝改善の新規治療戦略として、IGF-IがABCA1発現促進により、脂肪肝を抑制する可能性があるという仮説を実証し、成長ホルモン分泌不全症での臨床的課題である脂肪肝に対する有効な治療戦略となる可能性について基礎実験を通して証明できた本研究成果の社会的意義は大変大きいと考えられる。
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