Elucidation of the regulation mechanism of fatty acid metabolism in the EFAD state and its physiological significance

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K00848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Ochanomizu University
• Principal Investigator: Ichi Ikuyo お茶の水女子大学, 基幹研究院, 講師 (50403316)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 多価不飽和脂肪酸 / 必須脂肪酸欠乏 / 脂肪酸代謝 / 脂肪肝 / ミード酸

Outline of Final Research Achievements

In an essential fatty acid (EFA)-deficiency state, Mead acid (20:3n-9), is an unusual n-9 series polyunsaturated fatty acid (PUFA), which is endogenously synthesized from oleic acid (18:1n-9). Although Elovl5, a fatty acid elongase, has long been known to selectively elongate C18 and C20 PUFAs, it can use 18:1n-9 as a substrate for the synthesis of Mead acid under PUFA-deficient conditions. Further, we revealed a novel regulatory mechanism that the substrate preference of ELOVL5 was modified through phosphorylation. The function of Mead acid during EFA-deficiency is not known, but we showed that the inhibition of Mead acid synthesis induced hepatic triacylglycerol accumulation via the suppression of very low-density lipoprotein (VLDL) secretion in EFA-deficiency mice. From these results, it is possible that Mead acid functions as a substitute for the PUFA produced from EFAs in VLDL secretion during EFA-deficiency.

Free Research Field

栄養学

Academic Significance and Societal Importance of the Research Achievements

低栄養は様々な疾患の憎悪因子であり、高齢化が進むわが国においてその改善は重要な課題である。低栄養にはタンパク質の栄養が重要視されているが、脂質の栄養に関するエビデンスは不十分である。我々が食事から摂取しなければならない多価不飽和脂肪酸（PUFA）は生体の恒常性維持に重要で、欠乏するとミード酸という通常は存在しない内因性のPUFAが産生される。本研究ではこれまで不明であったミード酸の新たな産生機構と作用を明らかにした。これらの脂質の必要性を明らかにすることは、低栄養の病態において新たな治療へと繋がることが期待できる。