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Elucidation of the mechanism of cell death of adipocytes induced by osteocalcin

Research Project

Project/Area Number 18K17021
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57010:Oral biological science-related
Research InstitutionFukuoka Dental College

Principal Investigator

OTANI Takahito  福岡歯科大学, 口腔歯学部, 講師 (80759738)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsオステオカルシン / 脂肪細胞 / 細胞死 / 脂質代謝 / 細胞接着 / エピゲノム / シグナル伝達 / ネクロトーシス
Outline of Final Research Achievements

Osteocalcin that is the bone matrix protein plays an important role in glucose and energy metabolism. We have shown that osteocalcin promotes the expression of adiponectin activating glucose and lipid metabolism as well as the signaling pathway by which osteocalcin induces adiponectin expression in adipocytes. In this process, we revealed the signaling pathway by which high-dose osteocalcin allowed adipocytes to lead to necroptosis induced by direct cell-cell contact in 30% adipocytes. Further, it is also indicated that high-dose osteocalcin prevents hypertrophy of adipocytes by the regulation of several adhesion molecules.

Academic Significance and Societal Importance of the Research Achievements

申請者は高濃度GluOCによる脂肪細胞へのネクロトーシス誘導とその分子メカニズムを解明した。これにより、GluOCは脂肪細胞をアディポネクチンの発現亢進などを介して代謝的に活性化するだけでなく、その細胞数をも調節することで、組織レベルでそのボリュームを正常に保つことが示唆され、このGluOCのもつ多面的な効果には高い学術的意義がある。また、高濃度GluOCは脂肪細胞の接着タンパクの発現を調節することによって、脂肪細胞の肥大化を抑制することが示唆されることから、糖尿病および肥満に対する副作用の少ない予防治療薬の開発に繋がる発展性を有しており、社会的意義も高いと考える。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Adipocyte-specific GPRC6A ablation promotes diet-induced obesity by inhibiting lipolysis2021

    • Author(s)
      Mukai Satoru、Mizokami Akiko、Otani Takahito、Sano Tomomi、Matsuda Miho、Chishaki Sakura、Gao Jing、Kawakubo-Yasukochi Tomoyo、Tang Ronghao、Kanematsu Takashi、Takeuchi Hiroshi、Jimi Eijiro、Hirata Masato
    • Journal Title

      Journal of Biological Chemistry

      Volume: 296 Pages: 100274-100274

    • DOI

      10.1016/j.jbc.2021.100274

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The roles of osteocalcin in lipid metabolism in adipose tissue and liver2020

    • Author(s)
      Otani Takahito、Mizokami Akiko、Kawakubo-Yasukochi Tomoyo、Takeuchi Hiroshi、Inai Tetsuichiro、Hirata Masato
    • Journal Title

      Advances in Biological Regulation

      Volume: 78 Pages: 100752-100752

    • DOI

      10.1016/j.jbior.2020.100752

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GLP-1 signaling is required for improvement of glucose tolerance by osteocalcin. J. Endocrinol.2020

    • Author(s)
      Mizokami, A., Mukai, S., Gao, J., Kawakubo-Yasukochi, T., Otani, T., Takeuchi, H., Jimi, E., Hirata, M.
    • Journal Title

      Journal of Endocrinology

      Volume: 244 Issue: 2 Pages: 285-296

    • DOI

      10.1530/joe-19-0288

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Osteocalcin triggers Fas/FasL-mediated necroptosis in adipocytes regulated by the activation of p300.2018

    • Author(s)
      Otani, T., Matsuda, M., Mizokami, A., Kitagawa, N., Takeuchi, H., Jimi, E.,Inai, T., and Hirata, M.
    • Journal Title

      Cell Death Disease

      Volume: 9 Issue: 12 Pages: 1194-1210

    • DOI

      10.1038/s41419-018-1257-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脂肪細胞の「数と質」を改善するオステオカルシン2020

    • Author(s)
      大谷 崇仁
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 脂肪細胞を細胞死へと導く骨基質タンパクOsteocalcin2019

    • Author(s)
      大谷 崇仁
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Necroptosis of Adipocytes Induced by Osteocalcin2019

    • Author(s)
      Takahito Otani
    • Organizer
      Kyudai Oral Bioscience & OBT Research Center Joint International Symposium 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Programmed Necrosis of Adipocytes Induced by High-dose Osteocalcin2018

    • Author(s)
      Masato Hirata
    • Organizer
      WCP2018-18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] オステオカルシンによる脂肪細胞のネクロトーシス2018

    • Author(s)
      大谷崇仁
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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