Molecular mechanisms of disruption of intestinal-liver organ connections in polyunsaturated fatty acid deficiency

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K02383
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 08030:Family and consumer sciences, and culture and living-related
• Research Institution: Ochanomizu University
• Principal Investigator: Ikuyo Ichi お茶の水女子大学, 基幹研究院, 准教授 (50403316)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 多価不飽和脂肪酸 / 必須脂肪酸 / 欠乏 / 脂肪肝 / アレルギー

Outline of Final Research Achievements

In mammals, essential fatty acid deficiency (EFAD) leads to the production of endogenous polyunsaturated fatty acid (PUFA), known as Mead acid, but the function of Mead acid under EFAD conditions is not yet understood. In this study, we examined the effects of dietary and endogenous PUFA deficiency on hepatic lipid accumulation and the pathogenesis of food allergy in mice deficient in FADS2, fatty acid desaturase. The results showed that FADS2-deficient mice fed a PUFA-deficient diet showed a marked decrease in highly unsaturated fatty acids with high carbon and double bonds, and a marked accumulation of cholesterol in the liver and an increase in inflammation and fibrosis. The pathology of ovalubmin-induced food allergy was also exacerbated in the highly unsaturated fatty acid-deficient mice.

Free Research Field

脂質栄養学

Academic Significance and Societal Importance of the Research Achievements

これまで、非肥満者非アルコール性脂肪性肝疾患（NAFLD）患者は肥満NAFLD患者に比べて、全死因死亡率や肝臓疾患関連死亡率が2倍以上高いことが報告されており、近年、肥満を伴わないNAFLDが着目されている。本研究の成果より、高度不飽和脂肪酸欠乏による脂肪肝の悪化は低栄養性脂肪肝の新たな発症の要因となる可能性がある。低栄養の予防や改善は健康寿命の延伸に繋がるが、低栄養改善における脂質栄養の重要度は低いのが現状である。本研究の成果は、脂肪肝やアレルギーにおける高度不飽和脂肪酸の必要性を明らかにし、これらの食事療法において新たな知見を提示することが期待できる。