Introduction: We previously demonstrated that cardiac-specific overexpression of perilipin 2 (PLIN2-TG) induced cardiac steatosis and atrial fibrillation. The glucagon-like peptide-1(GLP-1) receptor agonists have a possible beneficial effect on cardiovascular morbidity and mortality. However, the effects of GLP-1 receptor agonists on perilipin 2-induced AF is still unknown. We investigated that effects of dulaglutide, a GLP-1 receptor agonist, on AF induction in PLIN2-TG mice.
Methods: Dulaglutide (0.5 mg/kg) or saline was subcutaneously injected every 4 days for 8 weeks in PLIN2-non TG (NTG) and PLIN2-TG mice. Eight weeks after dulaglutide or saline treatment started, left atrial electrical burst pacing (S1S1 = 20 ms) for 15 sec was performed for 10 times to induce AF and the frequency of induction of AF and its mean duration were measured in all mice. Atrial optical mapping was performed in isolated-perfused heart preparations.
Results: Dulaglutide significantly decreased the increases in frequency of AF induction and mean AF duration induced by the burst pacing in PLIN2-TG mice. Optical activation mapping demonstrated that dulaglutide improved the decreased atrial conduction velocity in isolated-perfused PLIN2-TG mouse heats.
Conclusion: These results indicate that dulaglutide inhibits PLIN2-induced AF through the improvement of atrial impulse conduction slowing. GLP-1 receptor agonists may be useful for inhibiting AF in patients with cardiac steatosis.