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The mechanism of lipid droplet formation

Research Project

Project/Area Number 18K07982
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKanto 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
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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 / 肝臓 / 非アルコール性脂肪性肝炎 / 脂質転移タンパク質 / リゾリン脂質アシル基転移酵素
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.

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。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2023 2022 2021 2020 2019 2018

All Journal Article (2 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] 生化学視点からの栄養学2023

    • Author(s)
      伊藤雅方
    • Journal Title

      関東学院大学人間環境研究所所報

      Volume: 21 Pages: 46-48

    • Related Report
      2022 Annual Research Report
  • [Journal Article] 脂質転移たんぱく質の機能について2021

    • Author(s)
      伊藤雅方
    • Journal Title

      関東学院大学教養学会年報

      Volume: 14 Pages: 17-18

    • Related Report
      2021 Research-status Report
  • [Presentation] 生化学視点からの栄養学2022

    • Author(s)
      伊藤雅方
    • Organizer
      人間環境研究所 2022年度 第2回研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Disruption of steroidogenic acute regulatory protein-related lipid transfer domain containing 10 (STARD10) prevents the development of nonalcoholic steatohepatitis (NASH)2021

    • Author(s)
      Ito M, Ohshima D, Mikami Y, Tomida T, Adachi-Akahane S
    • Organizer
      The 94th Annual Meeting of the Japanese Pharmacological Society
    • Related Report
      2020 Research-status Report
  • [Presentation] The role of steroidogenic acute regulatory protein-related lipid transfer domain containing 10(STARD10) in the development of nonalcoholic steatohepatitis (NASH)2020

    • Author(s)
      Ito M, Ohshima D, Tomida T, Mikami Y, Adachi-Akahane S
    • Organizer
      The 93rd Annual Meeting of the Japanese Pharmacological Society
    • Related Report
      2019 Research-status Report
  • [Presentation] 非アルコール性脂肪性肝炎(NASH)の発症における脂質転移タンパク質STARD10の役割2019

    • Author(s)
      伊藤雅方, 大島大輔, 冨田太一郎, 三上義礼, 赤羽悟美
    • Organizer
      第141日本薬理学会関東部会
    • Related Report
      2019 Research-status Report
  • [Presentation] STARD10 promotes lipid droplet formation cooperatively with LPCAT12019

    • Author(s)
      Ito M, Tomida T, Mikami Y, Ohshima D, Adachi-Akahane S
    • Organizer
      9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS2019)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脂質転移タンパク質とリゾリン脂質アシル基転移酵素による脂肪滴形成促進機構2019

    • Author(s)
      伊藤 雅方, 冨田 太一郎, 三上 義礼, 大島 大輔, 赤羽 悟美
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肝細胞脂肪滴形成における脂質転移タンパク質STARD10 (Steroidogenic acute regulatory protein-related lipid transfer domain containing 10) の役割について2018

    • Author(s)
      伊藤 雅方, 冨田 太一郎, 三上 義礼, 大島 大輔, 赤羽 悟美
    • Organizer
      第248回生理学東京談話会
    • Related Report
      2018 Research-status Report
  • [Presentation] 非アルコール性脂肪性肝炎モデルマウスを利用した脂肪滴形成におけるリン脂質転移タンパク質とリン脂質産生酵素の役割2018

    • Author(s)
      伊藤 雅方, 冨田 太一郎, 三上 義礼, 大島 大輔, 高橋 佳一, 進藤 英雄, 清水 孝雄, 赤羽 悟美
    • Organizer
      第41回 日本分子生物学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肝細胞における脂質転移タンパク質とPC産生酵素による脂肪滴形成促進機構2018

    • Author(s)
      伊藤 雅方, 冨田 太一郎, 三上 義礼, 大島 大輔, 赤羽 悟美
    • Organizer
      生理学研究所 研究会 2018「心臓・血管系の頑健性と精緻な制御を支える分子基盤の統合的解明」
    • Related Report
      2018 Research-status Report
  • [Presentation] Crucial role of STARD10 in regulating lipid storage in mouse model of nonalcoholic steatohepatitis (NASH)2018

    • Author(s)
      Ito M, Tomida T, Mikami Y, Murakami S, Adachi-Akahane S
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2024-01-30  

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