Novel mechanisms for fatty liver formation based on metabolic network among amino acids and nucleobases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yamanaka Daisuke 東京大学, 大学院農学生命科学研究科(農学部), 特任助教 (10553266)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脂肪肝 / NASH / アミノ酸 / 核酸 / アデニン / イノシン一リン酸IMP

Outline of Final Research Achievements

We have analyzed the mechanism of fatty liver formation induced by a low arginine diet, in which only arginine is deficient among the amino acids. Recently, we found that a decrease in adenine metabolic compounds, which are part of the nucleic acid metabolic system, may be essential for the low arginine diet-induced fatty liver. In this study, we analyzed the role of metabolic networks that induce such a decrease in the adenine metabolic system in fatty liver formation and NASH development. We found that among the adenine metabolic systems, inosine monophosphate (IMP) is particularly important in the formation of simple fatty liver induced by arginine deficiency, and that this metabolic system is not involved in the development of NASH in a NASH model, methionine choline deficiency.

Free Research Field

分子内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

アルコール多飲歴のない非アルコール性脂肪肝炎（NASH）は肝硬変や肝癌へと進行し得るが、治療法が確立されていないことが問題となっている。これまで、脂肪肝形成やNASH発症に関する分子機構の研究は、インスリン抵抗性や脂質異常、炎症などの観点から行われてきた。一方で本研究は、アミノ酸と核酸代謝系（特にアデニン代謝系）の脂肪肝形における役割を明らかにした点が新しく、学術的重要性が高い。またアデニン代謝系が単純脂肪肝の形成には関与するもののNASH発症には関与しない点は、NASHに遷移しない脂肪肝を特定する病態分類などに応用でき、社会的意義も大きい。