Development and application of efficient synthesis of anti-inflammatory fatty acids

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K14780
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 37010:Bio-related chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Yutaro Saito 東京大学, 大学院工学系研究科(工学部), 助教 (10846281)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 多価不飽和脂肪酸 / 脂質メディエーター / 炎症制御

Outline of Final Research Achievements

This study aimed at developing a method to synthesize polyunsaturated fatty acid metabolites efficiently and easily, and investigating mechanisms and structure-activity relationships of receptors related to inflammation. As a result, this study has successfully developed a methodology for the efficient synthesis of polyunsaturated fatty acid
and their metabolites by controlling the chain length, number and position of olefins, and terminal structures. Using this method, the synthesis of polyunsaturated fatty acids can be accomplished in half a day to several days, instead of the several weeks to several months required in the conventional methods. Furthermore, this method allowed us to evaluate the activation ability of the synthesized polyunsaturated fatty acids to GPCRs involved in inflammation, and to succeed in finding a fatty acid that strongly activates FFAR1/GPR40.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究で自在かつ簡便に合成可能となった多価不飽和脂肪酸およびその代謝物は、炎症を適切に制御できるツールになると期待される。炎症は、異物の侵入や組織損傷に対する生体防御機構であるが、慢性炎症へと発展してしまうことで疾患や機能不全を引き起こす。 このような不適切な炎症は、精神疾患、神経変性疾患、糖尿病、がん、感染症、循環器系疾患など多くの疾患において見られる。そのため、炎症を適切に抑制する必要がある。本研究で見出された炎症関連受容体FFFAR1/GPR40の活性化能と多価不飽和脂肪酸の分子構造との関連は、今後の炎症制御戦略の大きな知見になると期待される。