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Analysis of pathogenesis and molecular mechanisms of age-dependent fatty liver disease

Research Project

Project/Area Number 21K06544
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Kofuji Satoshi  東京医科歯科大学, 難治疾患研究所, 講師 (00508153)

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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords肝臓 / 脂肪化 / 加齢 / 老化 / アフリカメダカ
Outline of Research at the Start

加齢依存性の疾患研究は、高齢社会となった現代では急務となっている。近年、加齢依存的な脂肪性肝疾患が報告された。しかしながら、その詳細な病態および発症機構はほとんど不明である。そこで本研究ではこれらを明らかにすることを目的としている。老化研究で注目されているアフリカメダカをモデル生物として、加齢が引き起こす肝臓の変化を組織学的、遺伝学的、そして生化学的に解析する。

Outline of Final Research Achievements

With the advent of a satiation period and an aging population, the fatty liver has become a growing problem. Interestingly, age-dependent fatty liver has also been reported. Since fatty liver disease can develop fibrosis, which can lead to severe disease progression to cirrhosis and hepatocarcinoma, there is an urgent need to elucidate the pathogenesis of this disease. In this study, age-dependent diseases were analyzed using the African turquoise killifish, a model organism that has attracted attention in aging research because of its half-life span. From histological analysis of the liver, we found that African killifish livers develop fatty liver after hatching, that accumulated lipids disappear with aging, and that, conversely, fibrosis develops. These results suggest that the African killifish is a useful model for fatty liver analysis.

Academic Significance and Societal Importance of the Research Achievements

高齢社会である現代社会においては、加齢に伴う疾患の予防法または治療法の開発が急務である。本研究は加齢依存的な肝疾患の新たな治療法確立のための基盤研究である。そのため、 本研究を発展させることで学問的だけではなく、将来的にQuality of Lifeを高めることにも繋がりうる。

Report

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

    (17 results)

All 2024 2023 2022 2021

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (13 results)

  • [Journal Article] Lethal Phenotype-Based Database Screening Identifies Ceramide as a Negative Regulator of Primitive Streak Formation2023

    • Author(s)
      Pu Jing、Kofuji Satoshi、Okamoto-Uchida Yoshimi、Danzaki Keiko、Yu Ruoxing、Suzuki Akira、Kitajima Satoshi、Nishina Hiroshi
    • Journal Title

      Stem Cells

      Volume: 41 Issue: 12 Pages: 1142-1156

    • DOI

      10.1093/stmcls/sxad071

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish2022

    • Author(s)
      Shibata T, Kawana H, Nishino Y, Ito Y, Sato H, Onishi H, Kano K, Inoue A, Taketomi Y, Murakami M, Kofuji S, Nishina H, Miyazawa A, Kono N, Aoki J.
    • Journal Title

      Scientific reports

      Volume: 12 Issue: 1 Pages: 7312-7312

    • DOI

      10.1038/s41598-022-11002-4

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HBx and YAP expression could promote tumor development and progression in HBV-related hepatocellular carcinoma2022

    • Author(s)
      Oda Chiyumi、Kamimura Kenya、Shibata Osamu、Morita Shinichi、Tanaka Yuto、Setsu Toru、Abe Hiroyuki、Yokoo Takeshi、Sakamaki Akira、Kamimura Hiroteru、Kofuji Satoshi、Wakai Toshifumi、Nishina Hiroshi、Terai Shuji
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 32 Pages: 101352-101352

    • DOI

      10.1016/j.bbrep.2022.101352

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Collagen type I-mediated mechanotransduction controls epithelial cell fate conversion during intestinal inflammation2022

    • Author(s)
      Kobayashi S, Ogasawara N, Watanabe S, Yoneyama Y, Kirino S, Hiraguri Y, Inoue M, Nagata S, Okamoto-Uchida Y, Kofuji S, Shimizu H, Ito G, Mizutani T, Yamauchi S, Kinugasa Y, Kano Y, Nemoto Y, Watanabe M, Tsuchiya K, Nishina H, Okamoto R, Yui S.
    • Journal Title

      Inflammation and Regeneration

      Volume: 42 Issue: 1 Pages: 49-49

    • DOI

      10.1186/s41232-022-00237-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 加齢依存的神経機能低下による肝再生不全機構の解明2024

    • Author(s)
      小藤智史、長尾裕志、岡本―内田好海、仁科博史
    • Organizer
      第144回日本薬学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 成熟神経細胞機能低下による加齢依存性肝再生不全誘導機構の解明2023

    • Author(s)
      小藤智史、長尾裕志、仁科博史
    • Organizer
      2023年度 日本生化学会関東支部例会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Characterization of aging phenotypes in African turquoise killifish2023

    • Author(s)
      Chen Junjie, Satoshi Kofuji, Hiroshi Nishina
    • Organizer
      ファーマバイオフォーラム2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] Identification of metabolic pathways regulating early mouse embryogenesis2023

    • Author(s)
      Satoshi Kofuji, Jing Pu, Yoshimi Okamoto-Uchida, Keiko Danzaki, Hiroshi Nishina
    • Organizer
      第18回生命医科学研究所ネットワーク国際シンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] スフィンゴ脂質代謝は臓器形成に必須組織である原始線条形成を制御する2023

    • Author(s)
      小藤智史、Jing Pu、岡本-内田好海、檀崎敬子、仁科博史
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] スフィンゴ脂質代謝は臓器形成に必須組織である原始線条形成を制御する2022

    • Author(s)
      小藤智史、Jing Pu、仁科博史
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 肝再生における神経細胞内MKK-JNKシグナル経路の機能解明2022

    • Author(s)
      小藤智史、長尾裕志、仁科博史
    • Organizer
      第30回日本Cell Death学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 成熟神経細胞機能低下による加齢依存性肝再生不全誘導機構の解明2022

    • Author(s)
      小藤智史
    • Organizer
      第 3 回 細胞死コロキウム
    • Related Report
      2022 Research-status Report
  • [Presentation] The light-inducible genes Per2, Cry1a and Cry2a regulate oxidative status in zebrafish2021

    • Author(s)
      Satoshi Kofuji, Yikelamu Alifu, Sachi Sunaga, Mizuki Kusaba, Jun Hirayama, Hiroshi Nishina
    • Organizer
      第27回小型魚類研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] 核酸代謝リプログラミングと核小体の活性化2021

    • Author(s)
      小藤智史
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 胎生致死から読み解くマウス原始線条形成機構2021

    • Author(s)
      小藤智史
    • Organizer
      第2回細胞死コロキウム
    • Related Report
      2021 Research-status Report
  • [Presentation] Identification of metabolic pathways involved in murine primitive streak formation2021

    • Author(s)
      Jing Pu, Satoshi Kofuji, Hiroshi Nishina
    • Organizer
      第29回日本 Cell Death 学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 転写共役因子YAPはコリン代謝を活性化させることにより細胞競合を引き起こす2021

    • Author(s)
      小藤智史、須永沙智、仁科博史
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report

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

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