The biological significance of characteristic fatty acid composition of phosphatidylinositol

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20996
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy; Functional biochemistry
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: Imae Rieko 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (60584000)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ホスファチジルイノシトール / アラキドン酸 / 脂肪肝

Outline of Final Research Achievements

Arachidonic acid is the predominant fatty acid in the sn-2 position of PI in mammals. Loss of LPIAT1, an acyltransferase introducing arachidonic acid into the sn-2 position of PI, causes accumulation of neutral lipid in the adult mouse. To investigate the underlying molecular mechanisms, we developed the in vitro analysis system using cultured cells. We used the human hepatoma cell line Huh-7 and expression of LPIAT1 was reduced by siRNA transfection. The molecular species of PI containing arachidonic acid was reduced and triglyceride was accumulated, and these phenotypes were rescued by expression of siRNA-resistant LPIAT1. We also analyzed the major phospholipids and found that only the amount of PI was reduced by the repression of LPIAT1 expression.

Free Research Field

脂質生物学

Academic Significance and Societal Importance of the Research Achievements

近年、脂肪肝を発症する人が増加しているが、脂肪肝は肝硬変や肝癌の発症リスクを高めることが知られている。一方最近、ホスファチジルイノシトールにアラキドン酸を導入する脂肪酸転移酵素LPIAT1の一塩基多型が脂肪肝や肝障害の発症に関わることが相次いで報告され、LPIAT1の機能と脂肪肝発症との関連を明らかにすることは、脂肪肝の新たな発症メカニズムの発見に繋がると考えられる。本研究では、そのメカニズム解析の基盤として肝臓由来培養細胞を用いた評価系を構築し、分子機構を解析した。