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Investigation in the pathogenesis of metabolic syndrome with in vivo molecular imaging

Research Project

Project/Area Number 23591298
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionThe University of Tokyo

Principal Investigator

YAMASHITA Hiroshi  東京大学, 医学部附属病院, 講師 (50323572)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsメタボリックシンドローム / 生体分子イメージング / 慢性炎症 / 肥満 / 制御性B細胞 / インターロイキン10 / 脂肪組織 / 分子イメージング / 共焦点顕微鏡 / メタボリック症候群 / 免疫異常 / リモデリング / 糖尿病
Research Abstract

Obesity is known to induce local inflammation within adipose tissue that contributes to systemic metabolic abnormalities. We investigated the underlying mechanisms that modulate adipose inflammation. We identified Breg cells that produce interleukin-10 constitutively within adipose tissue. B cell-specific Il10 deletion enhanced adipose inflammation and insulin resistance in diet-induced obese mice, whereas adoptive transfer of adipose tissue Breg cells ameliorated those effects. Adipose environmental factors, including CXCL12 and free fatty acids, support Breg cell function, and Breg cell fraction and function were reduced in adipose tissue from obese mice and humans. Our findings indicate that adipose tissue Breg cells maintain homeostasis within adipose tissue and that Breg cell dysfunction contributes pivotally to the progression of adipose tissue inflammation in obesity and may play significant roles in the pathogenesis of metabolic syndrome.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (14 results)

All 2013 2012 2011

All Journal Article (5 results) (of which Peer Reviewed: 3 results) Presentation (9 results)

  • [Journal Article] Adipose natural regulatory B cells negatively control adipose tissue inflammation2013

    • Author(s)
      Nishimura S, Manabe I, Takaki S, Nagasaki M, Otsu M, Yamashita H, Sugita J, Yoshimura K, Eto K, Komuro I, Kadowaki T, Nagai R
    • Journal Title

      Cell Metab

      Volume: (Epub ahead of print)(PMID : 24209772)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Adipose natural regulatory B cells negatively control adipose tissue inflammation2013

    • Author(s)
      Nishimura S, Manabe I, Takaki S, Nagaskai M, Ostu M, Yamashita H, Sugita J, Yoshimura K, Eto K, Komuro I, Kadowaki T, Nagai R
    • Journal Title

      Cell Metabolism

      Volume: 18 Issue: 5 Pages: 759-766

    • DOI

      10.1016/j.cmet.2013.09.017

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling2012

    • Author(s)
      Nishimura S, Manabe I, Nagasaki M, Kakuta S, Iwakura Y, Takayama N, Ooehara J, Otsu M, Kamiya A, Petrich BG, Urano T, Kadono T, Sato S, Aiba A, Yamashita H, Sugiura S, Kadowaki T, Nakauchi H, Eto K, Nagai R
    • Journal Title

      Blood

      Volume: 119(PMID 22096246)

    • Related Report
      2013 Final Research Report
  • [Journal Article] In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling.2012

    • Author(s)
      Nishimura S, Manabe I, Nagasaki M, Yamashita H, Sugiura S, Kadowaki T, Nakauchi H, Eto K, Nagai R. and et al.
    • Journal Title

      Blood

      Volume: 119

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling2011

    • Author(s)
      S.Nishimura
    • Journal Title

      Blood

      Volume: 119 Issue: 8 Pages: 128-131

    • DOI

      10.1182/blood-2011-09-381400

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation Associated with Obesity2013

    • Author(s)
      Nisimura S, Nagasaki M, Manabe I, Eto K, Yamashita H, Komuro I, Nagai R
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      横浜(Featured Reserach Session)
    • Related Report
      2013 Final Research Report
  • [Presentation] Autotaxin Contributes to the Adipose Tissue Expansion and Inflammation in Diet-induced-obesity in Mice2013

    • Author(s)
      Nagasaki M, Nishimura S, Manabe I, Uno K, Yamashita H, Nagai R, Komuro I
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation Associated with Obesity (Featured Reserach Session)2013

    • Author(s)
      Nisimura S, Nagasaki M, Manabe I, Eto K, Yamashita H, Komuro I, Nagai R
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Adipose Tissue Remodeling and Malfunctioning in Obesity Associated with Chronic Inflammation and Local Immunity2012

    • Author(s)
      Nishimura S, Ngasaki M, Manabe I, Eto K, Yamashita H, Nagai R
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] In Vivo Imaging Visualizes Discoid Platelet Aggregations without Endothelium Disruption and Contribution of Inflammatory Cytokine and Integrin Signaling2012

    • Author(s)
      Nishimura S, Ngasaki M, Manabe I, Eto K, Yamashita H, Nagai R
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Adipose Tissue Remodeling and Malfunctioning in Obesity Associated with Chronic Inflammation and Local Immunity2012

    • Author(s)
      Nishimura S, Ngasaki M, Manabe I, Eto K, Nagai R
    • Organizer
      日本循環器学会
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Presentation] In Vivo Imaging Visualizes Discoid Platelet Aggregations without2012

    • Author(s)
      Nishimura S, Ngasaki M, Manabe I, Eto K, Nagai R
    • Organizer
      日本循環器学会
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Presentation] Adipose Tissue Remodeling and Malfunctioning in Obesity Based on Chronic Inflammation and Abnormal Local Immunity2011

    • Author(s)
      Nishimura S, Nagasaki M, Manabe I, Eto K, Yamashita H, Nagai R
    • Organizer
      第75回日本循環器学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] In Vivo Molecular Imaging Reveals Multi-cellular Kinetics of Developing Thrombus2011

    • Author(s)
      Nishimura S, Nagasaki M, Manabe I, Eto K, Yamashita H, Nagai R
    • Organizer
      第75回日本循環器学会学術集会
    • Place of Presentation
      横浜(Featured Research Session)
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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