Development of new prevention strategy of heart disease focusing on fatty acid metabolism and cardiac hormone FGF21

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K20107
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Ashikaga University (2021); Gunma University (2019-2020)
• Principal Investigator: Sunaga Hiroaki 足利大学, 工学部, 講師 (10760077)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脂肪酸代謝 / 心筋梗塞 / 心不全 / FGF21 / ケトン体

Outline of Final Research Achievements

We recently showed that fibroblast growth factor-21 (FGF21), anti-diabetic hormone predominantly produced by liver and adipose tissue, was also produced in the ischemic heart with increasing blood fatty acid concentration and contributed to induction of AMPK activity. Then, we found that both serum βOHB and FGF21 levels were significantly elevated in patients with heart failure compared with control group, and significant positive correlations of βOHB with FGF21. Given that oxidative stress is a key driver of heart disease and clear relevance to human pathologies, our findings suggest that increasing delivery of βOHB and FGF21 to the heart via AMPK/PPARα signaling pathway seems to be a promising therapeutic approach to heart disease.

Free Research Field

脂質代謝学

Academic Significance and Societal Importance of the Research Achievements

ケトン体は主に心臓や脳でエネルギー基質として利用されることは知られているが、ケトン体が心臓の脂肪酸代謝、エネルギー代謝および心疾患の病態形成におよぼす影響について、転写レベルでの研究はほとんど報告されていない。我々の結果から、FGF21とケトン体が心筋内の酸化ストレス応答因子の発現を制御するなど心筋保護的に作用することが明らかとなり、FGF21とケトン体が心疾患予防・治療の新たな標的因子となる可能性が示唆された。本研究成果により、内因性のFGF21発現を誘導するような脂質を基にした栄養療法や食品の発見、さらにはFGF21とケトン体を標的因子とした様々な臓器疾患の予防・治療への応用が期待される。