Age-related changes in lipid metabolism and pathogenic mechanisms due to reduced L-serine synthesis

Research Project

Project/Area Number	18K17950
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 59040:Nutrition science and health science-related
Research Institution	Keio University
Principal Investigator	Sayano Tomoko 慶應義塾大学, 医学部(信濃町), 特任助教 (20733934)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	セリン欠乏 / 脂質代謝 / コレステロール / 加齢 / 脂質代謝異常 / セリン
Outline of Final Research Achievements	To identify molecules affected by L-Serine (Ser) depletion and the molecular mechanism underlying the L-Ser deficiency-induced metabolic abnormalities, qPCR, Western blotting and LC-TOFMS was performed in this study. The results showed that L-Ser deficiency significantly alters metabolites related to Cholesterol, Fatty acid synthesis, and metabolic pathways. This indicates the role of L-Ser in maintaining cellular homeostasis.
Academic Significance and Societal Importance of the Research Achievements	セリン欠乏に連関した脂質代謝基盤が明らかになれば、アミノ酸欠乏が惹起する脂質代謝軸恒常性破綻が、従来病因の分子基盤が明らかになっていない神経変性疾患の新たな病因性として結びつけられると考えている。実際にアミノ酸代謝・スフィンゴ脂質代謝・コレステロール代謝の異常が原因となって発症することが示唆されている神経疾患は多く、これらの代謝軸の理解を目指す本研究は、代謝性神経疾患の病態解明とその治療戦略の構築に貢献できると期待している。