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Immune response to postprandial factors through activation of Akt in macrophages

Research Project

Project/Area Number 17K16141
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Metabolomics
Research InstitutionThe University of Tokyo

Principal Investigator

Toda Gotaro  東京大学, 医学部附属病院, 特任臨床医 (30780332)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords食後糖代謝 / 免疫 / サイトカイン / 肝糖新生 / 食後糖代謝調節 / 腸内細菌叢 / 発現調節 / インスリン / LPS / 代謝 / 環境
Outline of Final Research Achievements

Lipopolysaccharide (LPS), which has been reported to drive the pathogenesis of obesity, is also elevated in normal lean mice after feeding, raising the possibility of its role in maintaining postprandial glycemia. Among factors induced in macrophages by LPS, interleukin-10 (IL-10) was elevated in the portal vein after feeding. In vivo the IL-10 signal in liver was shown to suppress postprandial gluconeogenic gene expression. Interestingly, both insulin and LPS stimulation were required for the rapid induction of IL-10 in macrophages. Indeed, myeloid LPS and insulin/Akt/mTOR signaling were shown to be required for the induction of IL-10 in macrophages and the postprandial suppression of gluconeogenic genes in liver. In obese mice, replenishment of IL-10 by adenoviral gene transfer attenuated both postprandial glycemia and hyperinsulinemia. Our results suggested a therapeutic potential of postprandial Akt-mTOR mediated IL-10 production by macrophages in obesity.

Academic Significance and Societal Importance of the Research Achievements

免疫細胞が肥満状態で炎症を引き起こすことにより肥満を増悪させることは数多く報告されてきたが、本研究では正常な状態で免疫が食後の代謝を調節するプロセスを明らかにした。肥満の形成ではこの正常な機能が破綻することにより組織マクロファージでのIL-10欠乏が生じると考えられる。今後の検討によりその過程の詳細が明らかになれば、肥満・インスリン抵抗性に対する新たな治療ターゲットとなることが期待される。

Report

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

    (5 results)

All 2018 2017

All Presentation (5 results) (of which Int'l Joint Research: 3 results)

  • [Presentation] Macrophages React to Postprandial Signals and Regulate the Response to Feeding through Akt-mTOR Dependent Production of IL-10.2018

    • Author(s)
      Gotaro Toda
    • Organizer
      78th Scientific Sessions of the American Diabetes Association.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Akt in macrophages regulates postprandial glycemia through production of Interleukin-10.2018

    • Author(s)
      Gotaro Toda
    • Organizer
      Keystone Symposia, Drivers of Type 2 Diabetes: From Genes to Environment.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マクロファージは摂食時の腸内細菌由来 LPS シグナルに反応し Akt-mTOR を介した IL-10 発現により肝糖新生を抑制する.2018

    • Author(s)
      戸田郷太郎
    • Organizer
      第5回肝臓と糖尿病・代謝研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マクロファージは摂食時の体内変化に反応しAktを介して糖代謝を制御する2017

    • Author(s)
      戸田郷太郎
    • Organizer
      第60回 日本糖尿病学会年次学術集
    • Related Report
      2017 Research-status Report
  • [Presentation] Akt in Mcrophages Regulate the Response to Feeding2017

    • Author(s)
      戸田郷太郎
    • Organizer
      77th Scientific Sessions of the American Diabetes Association
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2020-03-30  

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