Physiological doses of eicosapentaenoic acid suppress high-fat diet–induced atrial fibrillation in mice independent of lipid lowering

Long-term treatment with eicosapentaenoic acid (EPA) has been reported to reduce the risk of atrial fibrillation (AF) in mice fed a high-fat diet (HFD); however, the appropriate dose required to attenuate atrial vulnerability to AF remains unclear. The present study aimed to determine whether different amounts of daily intake of EPA exert preventive effects against AF. We conducted a series of experiments in HFD-fed mice treated with either low-dose EPA (30 mg/kg) or high-dose EPA (300 mg/kg). Both EPA doses similarly shortened AF duration and improved atrial conduction, as assessed by P-wave duration on surface electrocardiography. Notably, neither low- nor high-dose EPA significantly improved HFD-induced dyslipidemia, and no difference in cholesterol-lowering effects was observed between the two EPA treatment groups. These findings suggest that physiologically relevant dietary intake of EPA is sufficient to prevent atrial arrhythmias and to ameliorate impaired atrial conduction associated with AF, independent of systemic lipid-lowering effects.