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Physiological functions of nuclear lipid droplets

Research Project

Project/Area Number 21K06733
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionSapporo Medical University

Principal Investigator

Ohsaki Yuki  札幌医科大学, 医学部, 教授 (00378027)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords脂肪滴 / 中性脂質 / PML / 核膜変形 / 核内構造体 / 核膜形態 / 液晶化
Outline of Research at the Start

脂肪滴は小胞体膜で合成された中性脂質をリン脂質一重膜が被って形成される、細胞質オルガネラである。一方で肝由来細胞、及び一部の非肝由来細胞では核内にも豊富に存在し、核内構造体のひとつPML小体と会合する。
本研究では(1)内核膜からの脂肪滴直接形成という、新規の核内脂肪滴形成機構の探索、(2)膜を持つ脂肪滴がPML小体など他の非膜性核内構造体の生理機能に及ぼす影響、(3)細胞質、核内脂肪滴の内部脂質の組成変化・液晶化が、実際に脂肪滴表層脂質・タンパク質の局在と活性に及ぼす影響の3項目の検証を通じて核内脂肪滴の新たな生理的意義を立証する。

Outline of Final Research Achievements

Lipid droplets (LD) composed of neutral lipids and phospholipids monolayer can exist not only in the cytoplasm but in the nucleus. We identified different nuclear LD biogenesis mechanisms; one is specific to hepatic cells in which nuclear LDs are derived from lipoprotein precursors in the ER lumen, and another is for general cells in which LDs can be formed by a series of the enzymes of neutral lipid synthesis in the inner nuclear membrane. As functions of nuclear LDs, they were involved in phosphatidylcholine de novo synthesis and ameliorated ER stress in hepatic cells. In glioma cells, nuclear LD-PML complex bodies were related in the transcriptions of several tumor promoting factors. On the other hands, we found that nuclear LDs are frequently formed in human hepatocytes derived from biopsy of patients with various types of hepatic diseases. Further, we also found a family of ER/nuclear membrane proteins that can regulate the amount of nuclear LDs and nuclear membrane invagination.

Academic Significance and Societal Importance of the Research Achievements

半世紀以上謎の構造であった核内脂肪滴の形成機構と複数の生理的意義を明らかにした。特異な疎水性構造であるが、表面にリン脂質一重膜を持つ脂肪滴は、従来の膜を持たない核内構造体(PML小体、核小体など)に新たな機能を付加する可能性があり、新たな創薬標的の基礎研究拡大が期待される。さらに実際の人肝疾患患者で高頻度に核内脂肪滴が形成されており、従来の脂肪肝指標である細胞質脂肪滴蓄積と必ずしも相関しなかったことからも、特定の肝疾患に対して新たな特徴として定義づけられれば、原因不明の肝炎等の鑑別診断、治療の一助となる可能性が高い。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (12 results) (of which Invited: 5 results) Remarks (1 results)

  • [Journal Article] Distinct features of two lipid droplets types in cell nuclei from patients with liver diseases2023

    • Author(s)
      Norihiro Imai, Yuki Ohsaki, Jinglei Cheng, Jingjing Zhang, Fumitaka Mizuno, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Takanori Ito , Yoji Ishizu, Takashi Honda, Masatoshi Ishigami, Hiroaki Wake, Hiroki Kawashima
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 6851-6851

    • DOI

      10.1038/s41598-023-33977-4

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modified thoracoabdominal nerve block through perichondrial approach (M-TAPA): an anatomical study to evaluate the spread of dye after a simulated injection in soft embalmed Thiel cadavers2023

    • Author(s)
      Sawada Atsushi、Kumita Sho、Nitta Asako、Ohsaki Yuki、Yamakage Michiaki
    • Journal Title

      Regional Anesthesia and Pain Medicine

      Volume: 0 Issue: 8 Pages: 1-5

    • DOI

      10.1136/rapm-2022-104275

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of superficial tissue and intermuscular connections on rectus femoris muscle shear modulus heterogeneity2023

    • Author(s)
      Kodesho Taiki、Kato Takuya、Nakao Gakuto、Yokoyama Yu、Saito Yuhei、Watanabe Kota、Ohsaki Yuki、Katayose Masaki、Taniguchi Keigo
    • Journal Title

      Journal of Ultrasound

      Volume: 0 Issue: 3 Pages: 1-6

    • DOI

      10.1007/s40477-022-00769-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel cell-based system to assay cell-cell fusion during myotube formation2022

    • Author(s)
      ISOBE Mari、SUZUKI Yumika、SUGIURA Hideshi、SHIBATA Masahiro、OHSAKI Yuki、KAMETAKA Satoshi
    • Journal Title

      Biomedical Research

      Volume: 43 Issue: 4 Pages: 107-114

    • DOI

      10.2220/biomedres.43.107

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2022-08-18
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oleic acid‐bound FABP7 drives glioma cell proliferation through regulation of nuclear lipid droplet formation2022

    • Author(s)
      Umaru Banlanjo Abdulaziz、Kagawa Yoshiteru、Ohsaki Yuki、Pan Yijun、Chen Chuck T.、Chen Daniel K.、Abe Toshiaki、Shil Subrata Kumar、Miyazaki Hirofumi、Kobayashi Shuhei、Maekawa Motoko、Yamamoto Yui、Wannakul Tunyanat、Yang Shuhan、Bazinet Richard P.、Owada Yuji
    • Journal Title

      The FEBS Journal

      Volume: 290 Issue: 7 Pages: 1798-1821

    • DOI

      10.1111/febs.16672

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxygen?Glucose Deprivation Decreases the Motility and Length of Axonal Mitochondria in Cultured Dorsal Root Ganglion Cells of Rats2022

    • Author(s)
      Kikuchi Shin、Kohno Takayuki、Kojima Takashi、Tatsumi Haruyuki、Ohsaki Yuki、Ninomiya Takafumi
    • Journal Title

      Cellular and Molecular Neurobiology

      Volume: 43 Issue: 3 Pages: 1267-1280

    • DOI

      10.1007/s10571-022-01247-y

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner2020

    • Author(s)
      Soltysik Kamil、Ohsaki Yuki、Tatematsu Tsuyako、Cheng Jinglei、Maeda Asami、Morita Shin-ya、Fujimoto Toyoshi
    • Journal Title

      Journal of Cell Biology

      Volume: 220 Issue: 1

    • DOI

      10.1083/jcb.202005026

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] 脂肪滴の核内での形成機構と生理機能の形態学 的解析2023

    • Author(s)
      大崎雄樹
    • Organizer
      日本顕微鏡学会第79回学術講演会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 脂肪滴の核内での生成機序と意義2023

    • Author(s)
      大崎雄樹
    • Organizer
      第67回日本生化学会北海道支部例会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 核内脂肪滴形成に関与する核膜形態維持分子2023

    • Author(s)
      大崎雄樹、和田亘弘、本城愛子、室松悠希
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 生体組織における脂肪滴の異所性形成の意義2023

    • Author(s)
      大崎雄樹、今井則博、程晶磊、阿久津典之、仲瀬裕志
    • Organizer
      第55回日本臨床分子形態学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 脂肪滴のDNA損傷修復機構への関与2023

    • Author(s)
      大崎雄樹、和田亘弘、菊池鴻太、酒井恒
    • Organizer
      第129回日本解剖学会総会・全国学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 脂肪滴の新たな核内生理機能プラットフォームとしての 可能性2023

    • Author(s)
      大﨑 雄樹、 和田 亘弘、 程 晶磊、 今井 則博
    • Organizer
      第128回日本解剖学会総会・全国学術集会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 核内脂肪滴の新規生理機能2022

    • Author(s)
      大﨑 雄樹、 今井 則博、 程 晶磊、 立松 寛人、 菊地 鴻太
    • Organizer
      第54回日本臨床分子形態学会総会・学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 核内脂肪滴形成を制御する新たな分子機序2022

    • Author(s)
      大﨑 雄樹
    • Organizer
      日本解剖学会第68回 東北・北海道連合支部学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 脂肪滴の核内での生理的意義2022

    • Author(s)
      大﨑 雄樹
    • Organizer
      第64回 日本脂質生化学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 脂肪滴の核内形成機序に影響する核膜形態制御分子の検索2022

    • Author(s)
      大崎 雄樹、立松 寛人、程 晶磊
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 核内脂肪滴形成に影響する核膜変形制御分子の探索2021

    • Author(s)
      大崎 雄樹、立松 寛人、程 晶磊
    • Organizer
      第62回日本組織細胞化学会総会・学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 核内脂肪滴代謝に影響をあたえる核膜形態変化2021

    • Author(s)
      大崎 雄樹、立松 寛人、程 晶磊
    • Organizer
      第94回日本生化学大会
    • Related Report
      2021 Research-status Report
  • [Remarks] 肝疾患における核内脂肪滴の特徴を解明 肝疾患の新たな診断・治療法開発の可能性に期待

    • URL

      https://web.sapmed.ac.jp/jp/news/press/bvrbcc0000002n7n.html

    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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