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Elucidation of molecular basis common to cardiovascular disorders associated with aging and metabolic syndrome

Research Project

Project/Area Number 15H04825
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cardiovascular medicine
Research InstitutionKeio University

Principal Investigator

SANO MOTOAKI  慶應義塾大学, 医学部(信濃町), 准教授 (30265798)

Research Collaborator SHIRAKAWA Kohsuke  慶應義塾大学, 医学部循環器内科研究室, 大学院生
YAMAMOTO Tsunehisa  慶應義塾大学, 医学部循環器内科研究室, 大学院生
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords免疫老化 / 肥満 / T細胞 / マクロファージ / 高脂肪食 / 内臓脂肪 / B細胞 / 養子免疫細胞移入 / 糖尿病 / 慢性炎症 / 老化 / オステオポンチン / 加齢 / 細胞老化 / メタボリックシンドローム
Outline of Final Research Achievements

Chronic inflammation in visceral adipose tissue (VAT) precipitates the development of cardiometabolic disorders. Here, we have determined that a high-fat diet (HFD) caused a preferential increase and accumulation of CD44hiCD62LloCD4+ T cells that constitutively express PD-1 and CD153 in VAT. These cells possessed characteristics of cellular senescence and produced large amounts of osteopontin (OPN) in a PD-1-resistant manner. The features of these T cells were highly reminiscent of senescence-associated CD4+ T cells that normally increase with age. Adoptive transfer of CD153+PD-1+CD44hiCD4+ T cells from HFD-fed WT, but not Spp1-deficient, mice into the VAT of lean mice fed a normal diet recapitulated the essential features of VAT inflammation and insulin resistance. Our results demonstrate that a distinct CD153+PD-1+CD44hiCD4+ T cell population causes VAT inflammation by producing large amounts of OPN. This finding suggests a link between visceral adiposity and immune aging.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (12 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Invited: 4 results) Book (4 results)

  • [Journal Article] 老化を進める悪玉物質とは2018

    • Author(s)
      佐野元昭
    • Journal Title

      医学のあゆみ

      Volume: 264(11) Pages: 958-960

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Negative legacy of obesity2017

    • Author(s)
      Shirakawa K, Endo J, Katsumata Y, Yamamoto T, Kataoka M, Isobe S, Yoshida N, Fukuda K, Sano M
    • Journal Title

      PLoS One

      Volume: 12(10) Issue: 10 Pages: e0186303-e0186303

    • DOI

      10.1371/journal.pone.0186303

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Obesity accelerates T-cell senescence in visceral adipose tissue2016

    • Author(s)
      Shirakawa K, Yan X, Shinmura K, Endo J, Kataoka M, Katsumata Y, Yamamoto T, Anzai A, Isobe S, Yoshida N, Itoh H, Manabe I, Sekai M, Hamazaki Y, Fukuda K, Minato N, and Sano M.
    • Journal Title

      J Clin Invest.

      Volume: 126 Issue: 12 Pages: 4626-4639

    • DOI

      10.1172/jci88606

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Diabetes and Heart Failure-From Clinical and Basic Research Point of View2017

    • Author(s)
      佐野元昭
    • Organizer
      第81回日本循環器病学会学術集会(AHA-JCS Joint symposium)
    • Place of Presentation
      金沢都ホテル(石川県金沢市)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Diabetes and Heart Failure-From Clinical and Basic Research Point of View-2017

    • Author(s)
      佐野元昭
    • Organizer
      第81回日本循環器病学会学術集会
    • Place of Presentation
      金沢都ホテル(石川県金沢市)
    • Year and Date
      2017-03-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 臓器老化による臓器間ネットワークの破綻を探る-免疫老化と肥満関連疾患-2016

    • Author(s)
      佐野元昭
    • Organizer
      第39回分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Invited
  • [Presentation] Functional importance of immune cells in the heart -T cell senescence & cardiovascular-metabolic disease2016

    • Author(s)
      佐野元昭
    • Organizer
      第80回日本循環器病学会学術集会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-03-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Molecular mechanism of obesity/T2DM-associated cardiomyopathy -from the point of view of T cell senescence-2016

    • Author(s)
      佐野元昭
    • Organizer
      第80回日本循環器病学会学術集会(AHA-JCS Joint Symposium)
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] 医学のあゆみ2016

    • Author(s)
      白川公亮、佐野元昭
    • Publisher
      医師薬出版株式会社
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Book] 内分泌・糖尿病・代謝内科2016

    • Author(s)
      佐野元昭
    • Publisher
      科学評論社
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Book] 老化制御と疾患-エイジング研究の進歩-2016

    • Author(s)
      佐野元昭
    • Publisher
      日本臨牀社
    • Related Report
      2016 Annual Research Report
  • [Book] 老化制御と循環器疾患-エイジング研究の進歩-2016

    • Author(s)
      佐野元昭
    • Publisher
      日本臨牀社
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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