Elucidation of the mechanism of increased risk of adult onset cardiovascular disease in low birth weight infants focusing on DNA methylation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08520
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kumamoto University
• Principal Investigator: Arima Yuichiro 熊本大学, 国際先端医学研究機構, 特任准教授 (60706414)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ケトン体代謝

Outline of Final Research Achievements

As a result of studies using a low birth weight mouse model, we clarified that ketone body synthesis was enhanced throughout the body during the neonatal period. While ketone bodies are known as an energy source during starvation, recent report reveals its impacts to the epigenetic modifications. Therefore, considering the possibility that ketone body metabolism is involved in epigenome changes such as DNA methylation, we proceeded with the creation of knockout mice for HMG-CoA synthase 2 (Hmgcs2), which is a rate-determining step enzyme for ketone body synthesis. Although the Hmgcs2 KO mouse did not show a lethal phenotype, it was revealed that fatty liver was exacerbated and that ketone body synthesis had a mitochondrial protective effect.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究を通じて、偶然にもケトン体代謝の新たな機能を知ることができた(Arima Y, Nature Metabolism 2021)。現在このモデルを用いてDNAメチル化やヒストン修飾の変化を解析中である。今後ケトン体代謝によるエピゲノム制御機構が明らかになることで、周産期環境ストレスがどのように遺伝子発現に影響し、将来の表現型に変化を加えるのか、明確な分枝基盤に基づいて説明することが可能となる。またケトン体代謝については健康や老化の観点からも注目されており、これらの健康長寿研究にたいしても、新たな解析ツールとして有用である。