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

• Project/Area Number: 15K01720
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Oita 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: ¥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.

Research Products

• [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
  • 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
  • Peer Reviewed
• [Journal Article] Macrophage Infiltration Into the Endothelium of Atrial Tissue in Atrial Fibrillation (2017)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Role of atrial endothelial cells in the development of atrial fibrosis and fibrillation in response to pressure overload (2017)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Glucose Fluctuations Aggravate Cardiac Susceptibility to Ischemia/Reperfusion Injury by Modulating MicroRNAs Expression (2016)
  • 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
  • Peer Reviewed / Open Access
• [Presentation] Infiltration of Epicardial Adipose Tissue into Atrium is Essential for Inflammatory Atrial Fibrosis : Novel Therapeutic Target for Atrial Fibrillation (2017)
  • Author(s): Abe I, Miyamoto S, Takahashi N
  • Organizer: 日本循環器学会総会
  • 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 Tissue (2017)
  • 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
  • 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
  • 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
  • Int'l Joint Research