Elucidation of the mechanism of cell death of adipocytes induced by osteocalcin
| Project/Area Number |
18K17021
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57010:Oral biological science-related
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
OTANI Takahito 福岡歯科大学, 口腔歯学部, 講師 (80759738)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(9 results)
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[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.
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Journal Title
Journal of Endocrinology
Volume: 244
Issue: 2
Pages: 285-296
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Cell Death Disease
Volume: 9
Issue: 12
Pages: 1194-1210
DOI
Related Report
Peer Reviewed / Open Access
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