2021 Fiscal Year Final Research Report

Elucidation of liver mitochondrial failure and autoinflammation with RNA-epigenetics caused by nutrient stress

Research Project

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Project/Area Number	19K11692
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 59040:Nutrition science and health science-related
Research Institution	Okayama University
Principal Investigator	TAKAYAMA Fusako 岡山大学, 医歯薬学域, 准教授 (10236367)
Co-Investigator(Kenkyū-buntansha)	合葉哲也岡山大学, 医歯薬学域, 准教授 (00231754) 古田和幸岡山大学, 医歯薬学域, 准教授 (50644936) 檜垣和孝岡山大学, 医歯薬学域, 教授 (60284080)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	NAFLD/NASH / RNAメチル化 / インフラマソーム / エピジェネティクス / 酸化ストレス / 自己炎症 / 食習慣 / ミトコンドリア
Outline of Final Research Achievements	Inadequate diets (high fat and high sugar diets, overeating habit) are well known as the nutrient stress to develop metabolic syndrome related diseases including NAFLD/NASH (excessive triglyceride accumulation in hepatocytes [ectopic fat morbidity]). Using NAFLD/NASH model [Japanese Patent No.５１０９１３４] rats, we exhibited for the first time that changes in 1) RNA methylation degree and 2) ALKBH expression, 3) inflammasome complex formation, in hepatocytes of rats. These results had high correlations with the mitochondrial metabolism failure, oxidative stress and the NAFLD/NASH severity. According to other advance studies with cell experiments, the RNA-epigenetics with 1) and 2) have abilities to reform inflammasome complex and mitochondria function. In summary, the RNA-epigenetics responded to the nutrient stress, could link to mitochondrial disorder and chronic inflammation, the common roots to exacerbate metabolic syndrome related diseases including NAFLD/NASH.
Free Research Field	健康機能解析
Academic Significance and Societal Importance of the Research Achievements	高脂肪と高糖含有食の摂取習慣 (偏った食習慣) やカロリー過剰摂取習慣などの栄養ストレスとメタボリックシンドローム疾病の因果関係は広く受入れられている。メタボリックシンドローム根底の生活習慣病発症・増悪化に共通するエネルギー代謝破綻と自己炎症に繋がるRNAメチル化修飾変化を、糖質・タンパク質・脂質の３大栄養素の代謝を担い手かつ栄養エネルギー代謝の司令塔臓器である肝臓の疾患NAFLD/NASH病態で明らかにできた本課題成果は学術的に新規性が高く、抗メタボリックシンドローム機能特性の新評価系の樹立や確たる治療薬のないNASH治療薬や技術の新提案に直結し、産業的かつ社会的に極めて有意義である。