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Metabolic flux analysis for the liver of mice administered with glucose

Research Project

Project/Area Number 17K14864
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biofunction/Bioprocess
Research InstitutionThe University of Tokyo

Principal Investigator

Ohno Satoshi  東京大学, 大学院理学系研究科(理学部), 助教 (60755734)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords代謝フラックス解析 / メタボローム分析 / プロテオーム分析 / 代謝工学 / 哺乳類 / 代謝光学 / システム生物学 / 生物・生体工学 / 生体生命情報学
Outline of Final Research Achievements

In this study, we developed novel methods for organs to estimate metabolic fluxes in a non-steady-state condition and to analyze the regulation of the flux. We applied the developed methods to the liver of mice administrated with glucose. we found that the gluconeogenesis flux in the livers during starvation was much larger than the glycolytic flux in the liver after glucose administration. Furthermore, the differences in metabolic flux between wild-type and obese mice were dependent on amounts of enzymes for most reactions, while a few reactions including glycogen metabolism showed flux differences between wild-type and obese mice dependent on amounts of substrate and product metabolites.
In addition, we also applied the method developed above to adipocyte cell lines and found that insulin activated the glycolytic flux in adipocytes by translocation of Glut4, while fluxes through TCA cycle remained almost constant.

Academic Significance and Societal Importance of the Research Achievements

本研究の意義は、世界に先駆けて、生体内臓器の非定常フラックス推定手法の基盤技術を確立することにある。確立する技術を用いれば、他の組織・疾患モデルマウス・食餌の組成・薬剤に関する代謝応答をフラックスレベルで詳細に計測することが可能となるため、医学や生理学の分野全体に渡る代謝研究の加速が期待できる。また、生物工学においても、同一の培養槽で複数種の微生物が存在する共培養プロセスは、血液と複数の臓器が存在する系と同様なので、本研究と同じ手法が利用可能だと期待できる。

Report

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

    (11 results)

All 2020 2019 2018 2017 Other

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

  • [Int'l Joint Research] University of Sydney(オーストラリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Sydney(オーストラリア)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Sydney(オーストラリア)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Dynamic 13C Flux Analysis Captures the Reorganization of Adipocyte Glucose Metabolism in Response to Insulin2020

    • Author(s)
      Quek Lake-Ee、Krycer James R.、Ohno Satoshi、Yugi Katsuyuki、Fazakerley Daniel J.、Scalzo Richard、Elkington Sarah D.、Dai Ziwei、Hirayama Akiyoshi、Ikeda Satsuki、Shoji Futaba、Suzuki Kumi、Locasale Jason W.、Soga Tomoyoshi、James David E.、Kuroda Shinya
    • Journal Title

      iScience

      Volume: 23 Issue: 2 Pages: 100855-100855

    • DOI

      10.1016/j.isci.2020.100855

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rate-oriented trans-omics: integration of multiple omic data on the basis of reaction kinetics2019

    • Author(s)
      Yugi Katsuyuki、Ohno Satoshi、Krycer James R.、James David E.、Kuroda Shinya
    • Journal Title

      Current Opinion in Systems Biology

      Volume: 15 Pages: 109-120

    • DOI

      10.1016/j.coisb.2019.04.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism2017

    • Author(s)
      James R. Krycer, Satoshi Ohnoら全21名
    • Journal Title

      Cell Reports

      Volume: 21 Issue: 12 Pages: 3536-3547

    • DOI

      10.1016/j.celrep.2017.11.085

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Regulation of metabolic fluxes in adipocytes with insulin2019

    • Author(s)
      Satoshi Ohno, Akiyoshi Hirayama, Tomoyoshi Soga, David E. James, Shinya Kuroda
    • Organizer
      第13回メタボロームシンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Metabolic flux changes over time and the regulatory mechanisms in insulin-stimulated adipocytes2019

    • Author(s)
      Satoshi Ohno, Lake-Ee Quek, James R. Krycer, Katsuyuki Yugi, Akiyoshi Hirayama, Tomoyoshi Soga, David E. James, Shinya Kuroda
    • Organizer
      20th International Conference On Systems Biology (ICSB2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インスリン刺激下の脂肪細胞の代謝フラックスおよびその調節の数理解析2019

    • Author(s)
      大野 聡
    • Organizer
      第4回生活習慣病とがんの代謝栄養メカニズム研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 13C-based dynamic metabolic flux analysis in insulin-stimulated adipocyte cell lines and systematic evaluation of regulation on the metabolism2018

    • Author(s)
      Satoshi Ohno, Lake-Ee Quek, James R. Krycer, Katsuyuki Yugi, Akiyoshi Hirayama, Tomoyoshi Soga, David E. James, Shinya Kuroda
    • Organizer
      Metabolic Engineering 12
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 代謝システムの理解と応用に向けた数理解析2017

    • Author(s)
      大野 聡
    • Organizer
      日本生物工学会【研究部会】バイオインフォマティクス相談部会 第一回勉強会
    • Related Report
      2017 Research-status Report
    • Invited

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

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