The mechanism of lipid droplet formation

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K07982
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kanto Gakuin University (2021-2022); Toho University (2018-2020)
• Principal Investigator: Ito Masanori 関東学院大学, 栄養学部, 准教授 (20459811)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 脂質 / 脂肪肝 / 肝炎 / NAFLD / NASH / 脂肪滴 / リン脂質 / ホスファチジルコリン

Outline of Final Research Achievements

Lipid droplet (LD) is surrounded by phospholipid monolayer mainly composed of phosphatidylcholine (PC). Steroidogenic acute regulatory protein-related lipid transfer domain containing 10 (STARD10) has been shown to transfer PC between membranes in vitro. Lysophosphatidylcholine acyltransferase1 (LPCAT1) catalyzes the conversion of lysoPC to PC. STARD10 and LPCAT1 were partly co-localized at the surface of LD. The number of small LDs was increased by LPCAT1 overexpression, while the number of large LDs was increased by the overexpression of both STARD10 and LPCAT1 in mouse hepatoma cells (Hepa1-6). The percentage of small LDs was significantly higher in Stard10 knockout Hepa1-6 cells than that of normal Hepa1-6 cells. In the liver of Stard10 knockout mice, the total LD area was smaller and the sphericity of LD was lower than those of wild type mice. These results indicate that STARD10 and LPCAT1 are involved in LD formation by regulating surface-to-volume ratio.

Free Research Field

栄養生化学、応用遺伝学

Academic Significance and Societal Importance of the Research Achievements

肥満人口の増加にともない非アルコール性脂肪性肝疾患(nonalcoholic fatty liver disease; NAFLD)及びNAFLDが進行した非アルコール性脂肪性肝炎 (Non-alcoholic steatohepatitis; NASH) が増加傾向にある。NASHは肝硬変・肝癌へと進行する。そのためNAFLD/NASHの予防法や診断法の確立が急務である。 本研究では脂肪滴表面を構成するリン脂質に着目した。その結果リン脂質を産生するLPCAT1とリン脂質を転移するSTARD10の協調による脂肪滴形成促進機構の存在が示唆された。これはNAFLD/NASHの病態の理解に貢献する。