Untargeted Lipidomics for Heart Failure Inhibitory Metabolites Produced by Microbiome

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20730
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Kitasato University
• Principal Investigator: Yasuda Shu 北里大学, 薬学部, 助教 (90824483)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: GPx4 / 腸内細菌 / リピドミクス / 過酸化脂質

Outline of Final Research Achievements

In a mouse model of heart failure in which heart-specific GPx4-deficient mice are fed a low vitamin E-added diet, it was found that antibiotics can suppress heart failure, but that a small amount of vitamin E is required for this suppression. We also performed untargeted lipidomics of the cecum contents, heart, and plasma of heart failure mice with a small amount of vitamin E in the diet (survived) and heart failure mice with no vitamin E in the diet (died), and analyzed the metabolites that were more abundant in the surviving mice, and found several candidate metabolites that may suppress this heart failure.

Free Research Field

脂質生化学

Academic Significance and Societal Importance of the Research Achievements

心不全は日本における主な死因の一つとして知られ、特にスポーツ選手などで見られる過度な運動時に急に生じる心不全は原因が明らかになっていない。脂質酸化依存的な細胞死はこの急性心不全に関与するとも言われ、本研究で用いた心臓特異的GPx4欠損マウスに低ビタミンE添加食を食べさせる心不全モデルは、心不全の分子メカニズムを明らかにできる可能性がある。
今回見出した、腸内細菌や腸内細菌由来の心不全を抑制する可能性のある代謝物群は、心不全の予防薬となる可能性があり、社会的意義は大きい。