Abstract 15228: Hyperleptinemia Exacerbates High Fat Diet-mediated Atrial Remodeling and Fibrillation
Introduction: Obesity is an independent risk factor of atrial fibrillation (AF). Although serum leptin levels have been reportedly up-regulated in subjects
with obesity and metabolic syndrome (leptin resistance), the relation of hyperleptinemia and AF remains to be solved.
Hypothesis: We tested the hypothesis whether hyperleptinemia could exacerbate high-fat-diet (HFD)-mediated AF.
Methods: Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob mice (Ob) were treated either with normal-fat-diet (NFD) or 60% HFD. Eight weeks later, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed. The effect of leptin antagonist (LAnt) was also examined using osmotic mini-pump in WT-HFD mice.
Results: 1) HFD increased body weight and plasma leptin concentration in WT mice (both p<0.01). 2) Masson trichrome staining revealed that heterogeneous interstitial LA fibrosis was evident in WT-HFD, which was not observed in Ob-HFD (p<0.05). Up-regulation of collagen1, α-SMA, TNF-α, and MCP-1 mRNA levels observed in WT-HFD mice LA, was attenuated in Ob-HFD mice. 3) While transesophageal burst pacing invariably induced AF (8/8, 100%) in WT-HFD mice, it induced AF less frequently (1/8, 12.5%) in Ob-HFD mice (p<0.01). 4) In isolated perfused heart experiments, interatrial conduction time was prolonged in WT-HFD mice, but not in Ob-HFD mice (p<0.05). 5) Western immunoblotting revealed up-regulated expressions of phosphorylated-calmodulin kinase II (p-CamKII) and Na+-Ca2+ exchanger in WT-HFD mice (both p<0.01). However, these changes were attenuated in Ob-HFD mice. 6) LAnt treatment for 4 weeks attenuated the AF inducibility assessed by transesophageal burst pacing (8/8 vs 2/8, p<0.05).
Conclusions: Our findings suggest that hyperleptinemia (leptin resistance) plays an essential role in HFD-mediated atrial remodeling and AF. Inhibition of leptin or leptin signaling may become a novel therapeutic target to prevent obesity-related AF.
Author Disclosures: Y. Ebata: None. A. Fukui: None. H. Kondo: None. S. Saito: None. I. Abe: None. K. Aoki: None. T. Shinohara: None. Y. Teshima: None. T. Saikawa: None. N. Takahashi: None.
- © 2014 by American Heart Association, Inc.