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Elucidation of physiological function of fatty liver-specific protein

Research Project

Project/Area Number 17K08799
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionFukuoka University

Principal Investigator

MATSUSUE KIMIHIKO  福岡大学, 薬学部, 教授 (10389364)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords脂肪細胞 / 糖代謝 / 3T3ーL1細胞 / ノックダウン / 脂肪肝 / shRNA / 核内受容体 / 肝臓
Outline of Final Research Achievements

To elucidate the physiological function of HPD1 highly expressed in fat-accumulated cells, we prepared HPD1-knockdown adipocytes (3T3-L1 cells). Genechip analysis was used to analyze the gene expression of HPD1 knockdown and control cell mRNAs. The genes causing change in the expression by the knockdown of HPD1 was lipid metabolism, glucose metabolism, cytokine receptor and cytoskeleton-related genes. In these genes, hexokinase (known as glucose kinase) was focused. The hexokinase in HPD1-knockdown adipocytes led to the significant decrease of mRNA and protein levels and also glucose kinase activity compared to that in control adipocytes. The subcellular localization of HPD1 was previously demonstrated as detectable proteins in the cytoskeleton-enriched fraction. These results suggest that HPD1 in adipocytes indirectly associates with transcriptional regulation of a large number of genes.

Academic Significance and Societal Importance of the Research Achievements

HPD1タンパクは、脂肪肝の肝実質細胞や脂肪細胞など高脂肪蓄積細胞に特異的に発現している。それゆえ、我々は本タンパクを介した肝臓及び脂肪組織における新しい脂肪蓄積シグナルの存在を予想した。予想に反して、当該研究の結果は糖代謝との関連性を示すものであるが、直接的あるいは間接的なHPD1を介した脂肪蓄積シグナルの同定は、過剰な脂肪蓄積が原因となる非アルコール性脂肪肝インスリン感受性ならびに肥満などの治療に対するターゲットとしての応用が期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results) Presentation (10 results)

  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Insulin induces expression of the hepatic <i>vaspin</i> gene2020

    • Author(s)
      Aibara, D. Matsuo, K. Yamano, S. Matsusue, K.
    • Journal Title

      Endocrine Journal

      Volume: 67 Issue: 1 Pages: 9-14

    • DOI

      10.1507/endocrj.EJ19-0276

    • NAID

      130007790983

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fat-specific protein 27b is regulated by hepatic peroxisome proliferator-activated receptor γ in hepatic steatosis2020

    • Author(s)
      Aibara, D. Matsuo, K. Yamano, S. Matsusue, K.
    • Journal Title

      Endocrine Journal

      Volume: 67 Issue: 1 Pages: 37-44

    • DOI

      10.1507/endocrj.EJ19-0296

    • NAID

      130007790974

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vaspin is a novel target gene of hepatic CCAAT-enhancer-binding protein2019

    • Author(s)
      Aibara, D. Matsuo, K. Yamano, S. Matsusue, K.
    • Journal Title

      Gene

      Volume: 721 Pages: 144113-144119

    • DOI

      10.1016/j.gene.2019.144113

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fat-specific protein 27 is a novel target gene of liver X receptor α.2018

    • Author(s)
      Aibara D, Matsusue K, Takiguchi S, Gonzalez FJ, Yamano S.
    • Journal Title

      Mol Cell Endocrinol

      Volume: 印刷中 Pages: 48-56

    • DOI

      10.1016/j.mce.2018.02.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Codeine 親電子性代謝物 Codeinone は Keap1/Nrf2 システムを活性化する2019

    • Author(s)
      松尾康平、 藍原大甫、 松末公彦、 山野茂
    • Organizer
      第 36 回日本薬学会九州支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Morphine 親電子性代謝物 Morphinone は Keap1/Nrf2 システムを活性化する2019

    • Author(s)
      松尾康平、 藍原大甫、 松末公彦、 山野茂
    • Organizer
      フォーラム 2019 衛生薬学・環境トキシコロジー
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂肪肝における Fsp27b 遺伝子の発現解析 ―PPARγによる発現制御―2018

    • Author(s)
      藍原大甫、松末公彦、瀧口総一、山野茂
    • Organizer
      第 35 回日本薬学会九州支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肝 C/EBPα の新規標的遺伝子 Serpina12 の同定と発現調節機構2018

    • Author(s)
      郡加寿美、藍原大甫、松末公彦、瀧口総一、山野茂
    • Organizer
      第 35 回日本薬学会九州支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 2 型糖尿病モデル ob/ob マウスの脂肪肝における Fsp27b 遺伝子の発現制御-PPARgammaの関与-2018

    • Author(s)
      藍原大甫、松末公彦、松尾康平、瀧口総一、山野茂
    • Organizer
      フォーラム 2018 衛生薬学・環境トキシコロジー
    • Related Report
      2018 Research-status Report
  • [Presentation] 再摂食時における肝 Fsp27 遺伝子の発現制御-インスリンの関与-2018

    • Author(s)
      藍原大甫、松末公彦、瀧口総一、山野茂
    • Organizer
      第138 年会日本薬学
    • Related Report
      2017 Research-status Report
  • [Presentation] 再摂食時の肝臓における Fsp27 遺伝子の発現解析-インスリンによる発現抑制-2017

    • Author(s)
      藍原大甫、松末公彦、松尾康平、瀧口総一、山野茂
    • Organizer
      第 34 回日本薬学会九州支部大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脂肪肝形成に関与する Fsp27 遺伝子のインスリンによる発現制御2017

    • Author(s)
      藍原大甫、松末公彦、瀧口総一、山野茂
    • Organizer
      フォーラム 2017 衛生薬学・環境トキシコロジー
    • Related Report
      2017 Research-status Report
  • [Presentation] 膵癌腹膜播種マウスモデルにおける crizotinib の抗腫瘍効果2017

    • Author(s)
      瀧口総一、松末公彦、寺本典弘、井口東郎
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Aldo-Keto Reductase (AKR) 1C12 と AKR1C13 の酵素化学的性質 -マウス肝 Morphine 6-Dehydrogenase との異同-2017

    • Author(s)
      松尾康平、立野愛美、松延祐衣、藍原大甫、松末公彦、 成松鎭雄、山野茂
    • Organizer
      第 44 回 日本毒性学会学術年会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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