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Elucidation of exosome-mediated crosstalk between adipose tissue and liver in nonalcoholic steatohepatitis

Research Project

Project/Area Number 19K17955
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Komiya Chikara  東京医科歯科大学, 医学部附属病院, 助教 (60825256)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsエクソソーム / miRNA / 肥満 / NASH / 非アルコール性脂肪肝炎 / 臓器連関
Outline of Research at the Start

肥満による脂肪組織炎症を起点とした脂肪組織-肝臓連関が非アルコール性脂肪肝炎(NASH)の病態形成に重要とされているが、その分子機構は不明な点が多い。エクソソームは、低酸素などの細胞環境に応じて放出される細胞外小胞で、放出細胞に由来するmiRNAなどが受容細胞に送達され、細胞間の情報伝達を担うことが明らかになってきた。本研究は、肥満による脂肪組織炎症の要因である低酸素応答に着目し、脂肪組織から放出されるエクソソームmiRNAがNASHの発症に関与する可能性についてマウスを用いて検討し、液性因子や神経による既存の機序では捉え切れなかった未知の脂肪組織-肝臓連関を見出す。

Outline of Final Research Achievements

Comprehensive analysis of serum exosomal miRNAs from obese mice using next-generation sequencing revealed that specific exosomal miRNAs are increased in obesity. Experiments with mice lacking a gene essential for hypoxic response in adipose tissue suggested that some of the increased exosomal miRNAs in obesity are possibly secreted from hypoxic adipose tissue. Although it was speculated that these exosomal miRNAs might be involved in crosstalk between adipose tissue and liver, animal studies indicated that they have a limited effect on the pathophysiology of NASH.

Academic Significance and Societal Importance of the Research Achievements

肥満において、血中のエクソソームが内包するmiRNAの変化を経時的に解析し、脂肪組織の低酸素応答により変化するものと変化しないものがあることを見出した。今後、個々のmiRNAについて、脂肪組織と肝臓の臓器連関への関与を検討することで、NASHに対する新たな治療標的の創出に繋がる可能性が期待できる。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Book (3 results)

  • [Journal Article] A case of ezetimibe-effective hypercholesterolemia with a novel heterozygous variant in ABCG52020

    • Author(s)
      Nakano Y, Komiya C, Shimizu H, Mishima H, Shiba K, Tsujimoto K, Ikeda K, Kashimada K, Dateki S, Yoshiura KI, Ogawa Y, Yamada T.
    • Journal Title

      Endocrine Journal

      Volume: 67 Issue: 11 Pages: 1099-1105

    • DOI

      10.1507/endocrj.ej20-0044

    • NAID

      130007945810

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sarcopenic obesity is associated with a faster decline in renal function in people with type 2 diabetes.2020

    • Author(s)
      Fukuda T, Bouchi R, Asakawa M, Takeuchi T, Shiba K, Tsujimoto K, Komiya C, Yoshimoto T, Ogawa Y, Yamada T.
    • Journal Title

      Diabet Med

      Volume: 37 Issue: 1 Pages: 105-113

    • DOI

      10.1111/dme.14153

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Book] 日本臨牀 増刊号 高血圧学 上2020

    • Author(s)
      小宮力、山田哲也
    • Total Pages
      6
    • Publisher
      日本臨牀社
    • Related Report
      2020 Annual Research Report
  • [Book] 医学のあゆみ エクソソームと疾患医学2020

    • Author(s)
      小宮力、山田哲也
    • Total Pages
      5
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2019 Research-status Report
  • [Book] 日本臨牀 NAFLD/NASH2019

    • Author(s)
      小宮力、小川佳宏、山田哲也
    • Total Pages
      7
    • Publisher
      日本臨牀社
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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