Lipid metabolism in the LC3 knockout mice

Research Project

Project/Area Number	17K08515
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	General anatomy (including histology/embryology)
Research Institution	Kagoshima University
Principal Investigator	Shibata Masahiro 鹿児島大学, 医歯学域医学系, 教授 (10343253)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	LC3 / カテプシンD / 脂質代謝 / 脂肪滴
Outline of Final Research Achievements	Autophagy is one of the bulk degradation systems in cells. LC3 is localized in the autophagosomal membrane so that it has been considered as a marker protein for autophagy. In this study, I examined the LC3 function in lipid metabolism using LC3 knockout mice. Adipose tissue mass in the mice deficient for LC3 having high fat diet was suppressed rather than in the control mice, and the lipid droplets in the cells differentiated into the adipocytes decreased rather than those derived from the control cells. Autophagy in the LC3 knockout mice crossed with the cathepsin D knockout mice, in which autophagy is increased, was not suppressed. These results indicate that LC3 would be compensated with other molecules in the course of autophagy.
Academic Significance and Societal Importance of the Research Achievements	オートファジーは細胞内の大規模タンパク分解系として知られている。今回LC3欠損マウスを用いることで、LC3が脂肪代謝に関与していることを示した。この結果には、脂質代謝のメカニズム解明という学術的意義があるだけでなく、脂質異常症の治療において貢献できるという臨床的な意義もある。さらに、オートファジー亢進モデルであるカテプシンD欠損マウスを交配させてもオートファジーが抑制されないことは、他の分子によってLC3が代償されていることを示し、細胞生物学の分野にとっても非常に意義深い結果である。