Comprehensive analysis of the metabolic pathway involved in the biological function of omega-3 fatty acids

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K18364
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy; Genome biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Ishihara Tomoaki 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (90724013)
• Research Collaborator: Arita Makoto ; Ikeda Kazutaka
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: ω3脂肪酸 / 脂肪酸代謝酵素 / 活性代謝物 / チトクロムP450 / 生体恒常性 / EPA / 17,18-EpETE

Outline of Final Research Achievements

Omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA), display a wide range of beneficial effects mediated through converting into bioactive lipid mediators by fatty acid oxygenases. It is reported that 17,18-epoxyeicosatetraenoic acid (17,18-EpETE), an epoxide form of EPA, has anti-inflammatory bioactivity against various inflammatory models. However, its metabolic pathway and its endogenous function in vivo remains unknown. In this study, we conducted a comprehensive analysis of murine fatty acid oxygenases to form 17,18-EpETE and revealed that five cytochrome P450 (Cyp) isoforms converted EPA into 17,18-EpETE. Next, we analyzed Cyp-deficient mice, and suggested not only that this Cyp is involved in omega-3 fatty acid metabolism, but also that bioactive metabolites produced by this enzyme may contribute to maintain tissue homeostasis in vivo.

Free Research Field

生物系薬学、脂質生物学

Academic Significance and Societal Importance of the Research Achievements

炎症反応は癌やアルツハイマー病の病態において重要な役割を果たしていると考えられている．また，近年の医療費増加は先進国において大きな問題になっているため，医療用医薬品に頼らない方法，特に食品（特定保健用食品や機能性表示食品）による疾患予防に大きな注目が集まっている．すなわち，本研究は長い間不明であったω3脂肪酸による炎症抑制機序の全体像を明らかにする技術基盤となる研究であるとともに，ω3脂肪酸食による疾病予防エビデンスを提供する社会的にも大変意義のある研究であると考えている．