2023 Fiscal Year Final Research Report
Clarify the role of mitochondria function on the development of fatty liver and hepatic carcinogenesis by targeting Apop-1
Project/Area Number |
21H03369
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 59040:Nutrition science and health science-related
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Research Institution | Mukogawa Women's University |
Principal Investigator |
FUKUO Keisuke 武庫川女子大学, 食物栄養科学部, 教授 (40156758)
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Co-Investigator(Kenkyū-buntansha) |
安田 修 鹿屋体育大学, スポーツ生命科学系, 教授 (00372615)
西川 浩樹 大阪医科薬科大学, 医学部, 教授 (30769609)
榎本 平之 兵庫医科大学, 医学部, 教授 (40449880)
大谷 直子 大阪公立大学, 大学院医学研究科, 教授 (50275195)
横路 三有紀 武庫川女子大学短期大学部, 食生活学科, 講師 (80757188)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | ミトコンドリア / 脂肪肝 / 肝発がん |
Outline of Final Research Achievements |
Chemically induced carcinogenesis in the liver was performed by DMBA and high fat diet in APOP1 KO and wild type mice. Compared with wild type mice, tumor formation was significantly suppressed and only a few malignant tumors were observed in APOP1 KO mice. Single cell RNA-seq analyses showed that signaling molecules of innate immunity were activated in liver tissues isolated from APOP1 KO. In clinical studies, APOP1 SNP analyses showed that NAFLD/NASH patients with minor allele had higher incidence of hepatic steatosis and higher content of fat as compared to NAFLD/NASH patients with major allele. In addition, higher fibrosis markers and lower numbers of platelets in major allele patients as compared with minor allele and these tendencies were stronger in male patients compared with female patients. These findings suggest that APOP1 SNP may be associated with development and progression in male patients with NAFLD/NASH.
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Free Research Field |
臨床栄養学
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、我々が発見したミトコンドリア蛋白質APOP1を標的として、脂肪肝からの肝発がん機序を明らかにするものである。高脂肪食誘導性肝がん発症モデルでは、APOP1 KOマウスはWTマウスに比し肝腫瘍形成が顕著に抑制されること、シングルセルRNA-seq解析により、APOP1 KOマウスでは自然免疫系のシグナル分子が活性化されていることを初めて明らかにした。また、NASH/NAFLD患者を対象としたAPOP1 SNPと脂肪化の程度や線維化マーカーや血小板の値などとの関係の解析から、APOP1 SNPがNAFLD/NASHの発症や進展に関連する可能性があることを初めて明らかにした。
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