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Preventoin of atrial fibrillation associated with obesity: Novel strategy targeting leptin

Research Project

Project/Area Number 15K01720
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionOita University

Principal Investigator

NAOHIKO TAKAHASHI  大分大学, 医学部, 教授 (30263239)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords心房細動 / 肥満 / レプチン / 線維化 / 心外膜脂肪 / 炎症性サイトカイン / 高レプチン血症 / 炎症
Outline of Final Research Achievements

BACKGROUND: Obesity including metabolic syndrome is an independent risk factor of atrial fibrillation (AF). We tested the hypothesis that high-fat diet (HFD)-induced hyperleptinemia exacerbates atrial fibrosis and AF. METHODS AND RESULTS: Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob (Ob) mice were treated with a normal-fat diet (NFD) or 60% HFD. While transesophageal burst pacing invariably induced AF (8/8, 100%) in WT-HFD mice, AF was induced less frequently (1/8, 12.5%) in Ob-HFD mice (P < 0.01). Masson's trichrome staining and the hydroxyproline assay revealed interstitial LA fibrosis in WT-HFD mice, which was not observed in Ob-HFD mice (P < 0.05). CONCLUSIONS: Our findings suggest that hyperleptinemia exacerbates HFD-mediated atrial fibrosis and AF. Inhibition of leptin signaling may become a novel therapeutic target to prevent obesity-related AF.

Report

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

    (9 results)

All 2017 2016

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

  • [Journal Article] Hyperleptinemia Exacerbates High-Fat Diet-Mediated Atrial Fibrosis and Fibrillation.2017

    • Author(s)
      Fukui A, Ikebe-Ebata Y, Kondo H, Saito S, Aoki K, Fukunaga N, Shinohara T, Masaki T, Teshima Y, Takahashi N.
    • Journal Title

      J Cardiovasc Electrophysiol.

      Volume: 印刷中 Issue: 6 Pages: 702-710

    • DOI

      10.1111/jce.13200

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible role of rivaroxaban in attenuating pressure-overload-induced atrial fibrosis and fibrillation.2017

    • Author(s)
      Kondo H, Abe I, Fukui A, Saito S, Miyoshi M, Aoki K, Shinohara T, Teshima Y, Yufu K, Takahashi N.
    • Journal Title

      J Cardiol

      Volume: 71 Issue: 3 Pages: 310-319

    • DOI

      10.1016/j.jjcc.2017.08.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage Infiltration Into the Endothelium of Atrial Tissue in Atrial Fibrillation2017

    • Author(s)
      Sonoda Y, Teshima Y, Abe I, Ebata Y, Oniki T, Kira S, Kondo H, Saito S, Yufu K, Miyamoto S, Shimada T, Takahashi N
    • Journal Title

      Circulation Journal

      Volume: 81 Issue: 11 Pages: 1742-1744

    • DOI

      10.1253/circj.CJ-16-1072

    • NAID

      130006179780

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of atrial endothelial cells in the development of atrial fibrosis and fibrillation in response to pressure overload2017

    • Author(s)
      Kume O, Teshima Y, Abe I, Ikebe Y, Oniki T, Kondo H, Saito S, Fukui A, Yufu K, Miura M, Shimada T, Takahashi N.
    • Journal Title

      Cariovasc Pathology

      Volume: 27 Pages: 18-25

    • DOI

      10.1016/j.carpath.2016.12.001

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Glucose Fluctuations Aggravate Cardiac Susceptibility to Ischemia/Reperfusion Injury by Modulating MicroRNAs Expression2016

    • Author(s)
      Saito S, Thuc LC, Teshima Y, Nakada C, Nishio S, Kondo H, Fukui A, Abe I, Ebata Y, Saikawa T, Moriyama M, Takahashi N.
    • Journal Title

      Circulation Journal

      Volume: 80 Issue: 1 Pages: 186-195

    • DOI

      10.1253/circj.CJ-14-1218

    • NAID

      130005116977

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Infiltration of Epicardial Adipose Tissue into Atrium is Essential for Inflammatory Atrial Fibrosis : Novel Therapeutic Target for Atrial Fibrillation2017

    • Author(s)
      Abe I, Miyamoto S, Takahashi N
    • Organizer
      日本循環器学会総会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Infiltration of Epicardial Adipose Tissue into Atrium Causes Inflammatory Atrial Fibrosis Possibly by Paracrine Effect : observation in Human Atrial Tissue2017

    • Author(s)
      Abe I, Teshima Y, Kaku H, Yonehara Y, Sonoda Y, Ikebe Y, Oniki T, Saito S, Kondo H, Akioka H, Shinohara T, Yufu K, Nakagawa M, Shimada T, Anai H, Miyamoto S, Takahashi N
    • Organizer
      日本循環器学会総会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Deletion of ghrelin exacerbates high fat diet-mediated atrial remodeling and fibrillation.2016

    • Author(s)
      Abe I, kaku H, Teshima Y, Sonoda Y, Ebata Y, Kondo H, Saito S, Shinohara T, Akioka H, Yufu K, Nakagawa M, Takahashi N.
    • Organizer
      第80回日本循環器学会学術集会
    • Place of Presentation
      宮城県仙台市 せんだい青葉山交流広場
    • Year and Date
      2016-03-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Spleen regulates M1/M2 macrophage homeostasis by the recruitment of dendritic cells in pressure-overloaded rat heart.2016

    • Author(s)
      Takano M, Kondo H, Saito S, Teshima Y, Yufu K, Nakagawa M, Takahashi N.
    • Organizer
      第80回日本循環器学会学術集会
    • Place of Presentation
      宮城県仙台市 せんだい青葉山交流広場
    • Year and Date
      2016-03-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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

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