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Non-invasive imaging of UCP1 expression in live mice

Research Project

Project/Area Number 16K08610
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionUniversity of Tsukuba

Principal Investigator

Fukuda Aya  筑波大学, 医学医療系, 准教授 (50436276)

Co-Investigator(Kenkyū-buntansha) 西村 健  筑波大学, 医学医療系, 准教授 (80500610)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsUCP1 / 褐色脂肪細胞 / ベージュ脂肪細胞 / イメージング / Ucp1 / iRFP / 蛍光イメージング / 褐色脂肪組織 / ベージュ脂肪組織 / ゲノム編集
Outline of Final Research Achievements

Uncoupling protein 1 (UCP1) is a mitochondrial protein that is expressed in both brown and beige adipocytes. UCP1 plays an important role in thermogenesis by uncoupling mitochondrial electron transport chain from ATP synthesis. Previous studies have shown that the Ucp1-deficient mice become sensitive to obesity while overexpression of UCP1 in adipose tissues prevents obesity, suggesting a role of UCP1 in the whole-body metabolism. To monitor the expression of UCP1 in a living animal non-invasively, we generated the Ucp1-iRFP720 knock-in mice, in which a near-infrared fluorescent protein iRFP720-coding gene is inserted into the Ucp1 gene locus. Using the mice, we observed strong fluorescence in the brown adipose tissues, and also detected the induction of beige adipocytes in the inguinal white adipose tissues of mice administered with a beta3 adrenoceptor agonist CL316243.

Academic Significance and Societal Importance of the Research Achievements

当研究で作製したUCP1イメージングマウスを用いると、従来のように動物から脂肪組織を取り出してUCP1の発現を解析する必要がなく簡便なうえ、さまざまな実験過程で起こりうる影響を排除できる。また、同一個体で継続的にUCP1の発現変動を解析できるため、個体差を考慮せずに長期的に解析できる。さらに、本マウスの脂肪組織から採取した脂肪幹細胞を用いてin vitroでUCP1の発現を誘導する薬剤をスクリーニングし、肥満治療薬の開発につなげることも将来的に可能である。以上の点から、本研究で作製したUCP1イメージングマウスは、世界的な肥満問題の解決につながる有意義なモデル動物である。

Report

(3 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(6 results)

All 2017 2016 Other

All Journal Article Presentation Remarks Patent(Industrial Property Rights)

  • [Journal Article] A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation.2017

    • Author(s)
      Nishimura K, Aizawa S, Nugroho FL, Shiomitsu E, Tran YTH, Bui PL, Borisova E, Sakuragi Y, Takada H, Kurisaki A, Hayashi Y, Fukuda A, Nakanishi M, Hisatake K
    • Journal Title

      Stem Cell Reports

      Volume: 8 Pages: 787-801

    • DOI

      10.1016/j.stemcr.2017.01.026

    • NAID

      120006224055

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] BMP-SMAD-ID promotes reprogramming to pluripotency by inhibiting p16/INK4A-dependent senescence2016

    • Author(s)
      Hayashi Y, Hsiao EC, Sami S, Lancero M, Schlieve CR, Nguyen T, Yano K, Nagahashi A, Ikeya M, Matsumoto Y, Nishimura K, Fukuda A, Hisatake K, Tomoda K, Asaka I, Toguchida J, Conklin BR, Yamanaka S
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 113(46) Pages: 13057-13062

    • DOI

      10.1073/pnas.1603668113

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] UCP1発現脂肪細胞の非侵襲イメージング法の作製2017

    • Author(s)
      本多志帆、福田綾、水野聖哉、杉山文博、岡松優子、斉藤昌之、林洋平、西村健、久武幸司
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Remarks] 筑波大学遺伝子制御学研究室HP

    • URL

      http://www.md.tsukuba.ac.jp/basic-med/biochem/gene/research3.html

    • Related Report
      2017 Research-status Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/basic-med/biochem/gene/research3.html

    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 遺伝子改変非ヒト動物及びその使用2017

    • Inventor(s)
      久武幸司、福田綾、本多志帆
    • Industrial Property Rights Holder
      久武幸司、福田綾、本多志帆
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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