Functional analysis of LPCAT3 in liver homeostasis and regeneration

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15074
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: INAGAKI NATSUKO 国立研究開発法人国立国際医療研究センター, その他部局等, 研究員 (00611419)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肝臓 / リン脂質 / 多価不飽和脂肪酸 / リゾリン脂質アシル転移酵素 / 肝再生 / メタボローム

Outline of Final Research Achievements

The liver has a remarkably high regenerative capacity that is regulated by several growth factors and signaling pathways working in a coordinated manner after liver resection to restore lost liver volume and function. Moreover, changes in membrane phospholipid composition have been reported during liver regeneration. However, the pathophysiological significance of these changes remains unknown. In this project, we focused on lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates arachidonic acid into lysophospholipids to produce phospholipids, and investigated whether qualitative and quantitative changes in membrane phospholipid composition might affect liver regeneration. Our study demonstrated that changes in membrane phospholipid composition allowed hepatocytes to prepare for the proliferation stage required for regeneration of liver tissue.

Free Research Field

肝臓学

Academic Significance and Societal Importance of the Research Achievements

LPCAT3は、2008年に研究代表者の所属研究室で単離された酵素であり、その生理学的機能や病態形成に果たす役割に関しては未解明な部分が多い。肝再生の観点からLPCAT3の恒常性維持機構については、これまで国内外においても報告例がなく、本研究成果によりLPCAT3が肝切除後肝再生における肝細胞の増殖に関与することを示すことが出来た。この成果は将来的に新規治療法などの開発へと発展しうる可能性が期待される。