Anti-inflammatory properties of lipid transfer protein in nonalcoholic steatohepatitis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19035
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Toho University
• Principal Investigator: ITO Masanori 東邦大学, 医学部, 講師 (20459811)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 炎症 / 肝臓 / 脂質転移タンパク質 / 脂肪蓄積 / 脂肪滴 / ホスファチジルコリン / リン脂質 / NASH

Outline of Final Research Achievements

NASH is characterized by lipid accumulation with inflammation and fibrosis in the liver. STARD10, steroidogenic acute regulatory protein-related lipid transfer domain containing 10, is a member of the START domain-containing lipid transfer protein family. To elucidate the role of STARD10 in lipid accumulation associated with NASH, NASH model mice were produced. The liver of Stard10 knockout(Stard10-/-) mice was smaller in size and the area of lipid droplet(LD) in hepatocytes was significantly smaller compared to those of WT mice. Gene expression levels of proinflammatory cytokines and fibrosis marker genes were lower in the liver of Stard10-/- mice. LD surface membrane consists of a single monolayer of phospholipids such as phosphatidylcholine(PC). Importantly, we found that STARD10 promotes the formation of large LDs through the interaction with lysophosphatidylcholine acyltransferase(LPCAT1). These results indicate that STARD10 and LPCAT1 play crucial roles in promoting LD formation.

Free Research Field

統合生理学、応用遺伝学、分子生物学