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Transomics analysis of glucose-responsive metabolic regulation through crosstalk between the liver and muscle and its alterations associated with obesity

Research Project

Project/Area Number 21K16349
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionNara Institute of Science and Technology

Principal Investigator

Kokaji Toshiya  奈良先端科学技術大学院大学, データ駆動型サイエンス創造センター, 助教 (80822551)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywordsトランスオミクス / 臓器連関 / 肥満 / インスリン / マルチオミクス
Outline of Research at the Start

肥満は、複数の臓器の適切な代謝制御とそれらの臓器間代謝サイクルを乱し、高血糖、高脂血症、2型糖尿病など代謝疾患を引き起こす。臓器代謝及び臓器間代謝サイクルはDNA・RNA・タンパク質・代謝物の各オミクス階層にまたがるトランスオミクスネットワークにより制御されており、未だその制御の全貌は明らかではない。本研究では、糖投与後の野生型マウスとレプチン欠損肥満マウスそれぞれについて、肝臓と骨格筋の代謝制御ネットワークを統合した肝臓筋肉連関トランスオミクスネットワークの構築を試みる。これにより肥満による肝臓筋肉間代謝サイクル異常およびそれらの原因となる上流因子の大規模な同定を目指す。

Outline of Final Research Achievements

To understand the mechanism of dysfunction of the inter-organ metabolic cycle in obesity, we constructed metabolic regulatory networks of liver and muscle, which are major glucose metabolizing organs, in wild-type mice and obesity model mice, and integrated them to construct a transomic network that crosses the liver and muscle.
As a result, we newly constructed a muscle glucose responsive transomic network, which can be compared and integrated with the liver network. We found that metabolites themselves do not regulate metabolism in the muscle of obese mice, but are instead regulated by gene expression.

Academic Significance and Societal Importance of the Research Achievements

肥満により肝臓や筋肉に脂肪が蓄積すると、糖や脂質の代謝制御がうまくいかず、血液中のグルコース濃度や脂質濃度が異常に高まり、動脈硬化など様々な疾患の原因となります。本研究では、グルコース投与という摂食に近い条件での筋肉における代謝制御ネットワークを初めて大規模に明らかにし、肝臓ネットワークとの統合により血糖及び血中脂質の恒常性の破綻メカニズムの全容が明らかとなることが期待されます。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (8 results)

All 2024 2023 2022

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (1 results)

  • [Journal Article] Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity.2024

    • Author(s)
      Bai Y, Morita K, Kokaji T, Hatano A, Ohno S, Egami R, Pan Y, Li D, Yugi K, Uematsu S, Inoue H, Inaba Y, Suzuki Y, Matsumoto M, Takahashi M, Izumi Y, Bamba T, Hirayama A, Soga T, Kuroda S*.
    • Journal Title

      iScience

      Volume: 27(3) Issue: 3 Pages: 109121-109121

    • DOI

      10.1016/j.isci.2024.109121

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acquisition of neural fate by combination of BMP blockade and chromatin modification2023

    • Author(s)
      Ong Agnes Lee Chen、Kokaji Toshiya、Kishi Arisa、Takihara Yoshihiro、Shinozuka Takuma、Shimamoto Ren、Isotani Ayako、Shirai Manabu、Sasai Noriaki
    • Journal Title

      iScience

      Volume: 26 Issue: 10 Pages: 107887-107887

    • DOI

      10.1016/j.isci.2023.107887

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle2023

    • Author(s)
      Maehara H.、Kokaji T.、Hatano A.、Suzuki Y.、Matsumoto M.、Nakayama K. I.、Egami R.、Tsuchiya T.、Ozaki H.、Morita K.、Shirai M.、Li D.、Terakawa A.、Uematsu S.、Hironaka K.、Ohno S.、Kubota H.、Araki H.、Miura F.、Ito T.、Kuroda S.
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 19118-19118

    • DOI

      10.1038/s41598-023-46393-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optogenetic decoding of Akt2-regulated metabolic signaling pathways in skeletal muscle cells using transomics analysis2023

    • Author(s)
      Kawamura Genki、Kokaji Toshiya、Kawata Kentaro、Sekine Yuka、Suzuki Yutaka、Soga Tomoyoshi、Ueda Yoshibumi、Endo Mizuki、Kuroda Shinya、Ozawa Takeaki
    • Journal Title

      Science Signaling

      Volume: 16 Issue: 773 Pages: 773-773

    • DOI

      10.1126/scisignal.abn0782

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of hepatic responses to glucose perturbation between healthy and obese mice based on the edge type of network structures2023

    • Author(s)
      Ito Yuki、Uda Shinsuke、Kokaji Toshiya、Hirayama Akiyoshi、Soga Tomoyoshi、Suzuki Yutaka、Kuroda Shinya、Kubota Hiroyuki
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 4758-4758

    • DOI

      10.1038/s41598-023-31547-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states.2022

    • Author(s)
      Kokaji T, Eto M, Hatano A, Yugi K, Morita K, Ohno S, Fujii M, Hironaka KI, Ito Y, Egami R, Uematsu S, Terakawa A, Pan Y, Maehara H, Li D, Bai Y, Tsuchiya T, Ozaki H, Inoue H, Kubota H, Suzuki Y, Hirayama A, Soga T, Kuroda S.
    • Journal Title

      Sci Rep

      Volume: 12 Issue: 1 Pages: 13719-13719

    • DOI

      10.1038/s41598-022-17964-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trans-omics analysis of insulin action reveals a cell growth subnetwork which co-regulates anabolic processes2022

    • Author(s)
      Terakawa Akira、Hu Yanhui、Kokaji Toshiya、Yugi Katsuyuki、Morita Keigo、Ohno Satoshi、Pan Yifei、Bai Yunfan、Parkhitko Andrey A.、Ni Xiaochun、Asara John M.、Bulyk Martha L.、Perrimon Norbert、Kuroda Shinya
    • Journal Title

      iScience

      Volume: 25 Issue: 5 Pages: 104231-104231

    • DOI

      10.1016/j.isci.2022.104231

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] マウスの肝臓と骨格筋における臓器内および臓器間代謝制御とその肥満による制御異常のトランスオミクス解析2022

    • Author(s)
      小鍛治俊也, 幡野敦, 伊藤有紀, 柚木克之, 衛藤樹, 守田啓悟, 大野聡, 藤井雅史, 廣中謙一, 江上陸, 寺川瑛, 土屋貴穂, 尾崎遼, 井上啓, 宇田新介, 久保田浩行, 鈴木穣, 池田和貴, 有田誠, 松本雅記, 中山敬一, 平山明由, 曽我朋義, 黒田真也
    • Organizer
      第45回日本分子生物学年会
    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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