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Analysis of regulation of lipid metabolism by vitamin D metabolite

Research Project

Project/Area Number 26350972
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical biology
Research InstitutionHokkaido University (2015-2016)
Kyoto University (2014)

Principal Investigator

WATANABE Mizuki  北海道大学, 薬学研究院, 講師 (20507173)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsビタミンD / 脂質代謝 / SREBP / SCAP
Outline of Final Research Achievements

This study revealed that an endogenous vitamin D metabolite suppresses the lipid biosynthesis. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that control lipid homeostasis. We screened a chemical library of endogenous molecules and identified 25-hydroxyvitamin D (25OHD) as an inhibitor of SREBP activation. Unlike sterols and other SREBP inhibitors, 25OHD impairs SREBP activation by inducing proteolytic processing and ubiquitin-mediated degradation of SCAP, thereby decreasing SREBP levels independently of the vitamin D receptor. Vitamin D supplementation has been proposed to reduce the risk of metabolic diseases, but the mechanisms are unknown. The present results suggest a previously unrecognized molecular mechanism of vitamin D-mediated lipid control that might be useful in the treatment of metabolic diseases.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (20 results)

All 2017 2016 2015 2014 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Invited: 2 results) Remarks (2 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 4 results)

  • [Journal Article] Vitamin D metabolite, 25-Hydroxyvitamin D, regulates lipid metabolism by inducing degradation of SREBP/SCAP.2017

    • Author(s)
      Asano, L., Watanabe, M., Ryoden, Y., Usuda, K., Yamaguchi, T., Khambu, B., Takashima, M., Sato, S., Sakai, J., Nagasawa, K., Uesugi, M.
    • Journal Title

      Cell Chem Biol.

      Volume: 24 Issue: 2 Pages: 207-217

    • DOI

      10.1016/j.chembiol.2016.12.017

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Synthesis of mevalonate- and fluorinated mevalonate prodrugs and their in vitro human plasma stability2015

    • Author(s)
      Kang, S.; Watanabe, M.; Jacobs, J.C.; Yamaguchi, M.; Dahesh, S.; Nizet, V.; Leyh, T. S.; Silverman, R.B.
    • Journal Title

      Eur. J. Med. Chem.

      Volume: 90 Pages: 448-461

    • DOI

      10.1016/j.ejmech.2014.11.040

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Live-cell Imaging of Endogenous mRNAs with a Small Molecule2015

    • Author(s)
      Sato, S.*, Watanabe, M., Katsuda, Y., Murata, A., Wang, D. O., Uesugi M.
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 54 Issue: 6 Pages: 1855-1858

    • DOI

      10.1002/anie.201410339

    • NAID

      120005619801

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthetic molecules that protect cells from anoikis and their use in cell transplantation2014

    • Author(s)
      Frisco-C., H.L.; Watanabe, M.; Okumura, N.; Kusamori, K.; Takemoto, N.; Takaya, J.; Sato, S.; Yamazoe, S.; Takakura, Y.; Kinoshita, S.; Nishikawa, M.; Koizumi, N.; Uesugi, M.
    • Journal Title

      Angew. Chem., Int. Ed.

      Volume: 53 Issue: 42 Pages: 11208-11213

    • DOI

      10.1002/ange.201405829

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 25‐ヒドロキシビタミンDによるSREBP-SCAPの分解メカニズムの解明2017

    • Author(s)
      浅野理沙、渡邉瑞貴、領田優太、長澤和夫、上杉志成
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学(宮城県仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 25‐ヒドロキシビタミンDによるSCAP/SREBPの分解メカニズムの解明2016

    • Author(s)
      浅野理沙、渡邉瑞貴、領田優太、長澤和夫、上杉志成
    • Organizer
      第58回天然有機化合物討論会
    • Place of Presentation
      東北大学(宮城県仙台市)
    • Year and Date
      2016-09-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 細胞内Ca2+動員情報伝達系の機構解明を目指した環状ADP-リボース誘導体の設計と合成2016

    • Author(s)
      渡邉瑞貴、佐藤隆俊、加藤広太郎、福田隼、村山尚、東田陽博、周東智
    • Organizer
      日本ケミカルバイオロジー学会第11回年会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] ケミカルバイオロジーによるビタミンD誘導体の新機能研究2016

    • Author(s)
      渡邉瑞貴
    • Organizer
      日本薬学会 第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 内因性小分子による脂質生合成抑制機構の解明2015

    • Author(s)
      渡邉瑞貴、浅野理沙、領田優太、薄田晃佑、 飯田圭介、佐藤慎一、長澤和夫、上杉志成
    • Organizer
      日本ケミカルバイオロジー学会 第10回年会
    • Place of Presentation
      東北大学百周年記念会館 川内萩ホール(宮城県仙台市)
    • Year and Date
      2015-06-11
    • Related Report
      2015 Research-status Report
  • [Presentation] ビタミン D 誘導体のケミカルバイオロジー研究2015

    • Author(s)
      渡邉瑞貴
    • Organizer
      第1回 有機化学を基盤とした創薬研究シンポジウム
    • Place of Presentation
      定山渓ホテル(北海道札幌市)
    • Year and Date
      2015-05-23
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 内因性低分子化合物による新規脂質代謝制御メカニズムの解明2015

    • Author(s)
      浅野理沙
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 脂質生合成を抑制する内因性小分子化合物2014

    • Author(s)
      渡邉瑞貴
    • Organizer
      第56回天然有機化合物討論会
    • Place of Presentation
      高知
    • Year and Date
      2014-10-15 – 2014-10-17
    • Related Report
      2014 Research-status Report
  • [Presentation] 内在性mRNA細胞内動態の新規イメージング法の開発2014

    • Author(s)
      佐藤慎一
    • Organizer
      第8回バイオ関連化学シンポジウム
    • Place of Presentation
      岡山
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] アノイキス抑制合成分子とその細胞移植への利用2014

    • Author(s)
      Frisco-C., Heidie L.
    • Organizer
      日本ケミカルバイオロジー学会第9回年会
    • Place of Presentation
      大阪
    • Year and Date
      2014-06-11 – 2014-06-13
    • Related Report
      2014 Research-status Report
  • [Remarks] 京都大学ホームページ 研究成果

    • URL

      http://www.kyoto-u.ac.jp/ja/research/research_results/2016/170127_1.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 日本の研究.com プレスリリース

    • URL

      https://research-er.jp/articles/view/54774

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] Compositions and methods for the treatment of metabolic disorders2016

    • Inventor(s)
      上杉志成、渡邉瑞貴、他
    • Industrial Property Rights Holder
      上杉志成、渡邉瑞貴、他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-05-24
    • Acquisition Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Vitamin D3 derivatives and pharmaceutical use thereof2014

    • Inventor(s)
      渡邉瑞貴、浅野理沙、長澤和夫、上杉志成
    • Industrial Property Rights Holder
      渡邉瑞貴、浅野理沙、長澤和夫、上杉志成
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-12-24
    • Related Report
      2014 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] Compositions and methods for the treatment of metabolic disorders2014

    • Inventor(s)
      上杉志成、渡邉瑞貴、他
    • Industrial Property Rights Holder
      上杉志成、渡邉瑞貴、他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-06-20
    • Related Report
      2014 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] Preparation of fatostatin A and derivatives and compositions thereof for the treatment of obesity2014

    • Inventor(s)
      上杉志成、渡邉瑞貴、他
    • Industrial Property Rights Holder
      上杉志成、渡邉瑞貴、他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-05-05
    • Related Report
      2014 Research-status Report
    • Overseas

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Published: 2014-04-04   Modified: 2018-03-22  

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