Role of Leptin Signaling in Pathogenesis of Atrial Fibrosis and Fibrillation

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Background: It has been reported that metabolic syndrome is associated with increased risk of atrial fibrillation (AF). Leptin exerts cardiovascular activity, which has not yet fully understood. Objectives: Here we tested the hypothesis weather leptin signaling would contribute to atrial fibrosis and AF evoked by the activation of rennin-angiotensin system. Method: Eight weeks old male CL57/B6Jmice (CNT) and aged-matched ob/ob mice (leptin deficient) were subcutaneously infused with angiotensin II (ATII, 2.0 mg/kg/day) or vehicle (VEH) via an osmotic minipump for two weeks. Transesophageal atrial pacing was preformed to induce AF. Results: Transesophageal pacing induced AF in all CNT-ATII mice (8/8, 100%), while it did not induce any AF in other three groups (CNT-VEH, ob/ob-ATII and ob/ob-VEH groups, p<0.01). Masson trichrome staining revealed that continuous ATII infusion caused inhomogeneous interstitial fibrosis in CNT-ATII group LA. However, it did not cause such fibrosis in ob/ob-ATII group LA (p<0.05). Conclusions: Our results firstly demonstrated that leptin signaling is indispensable for the development of atrial fibrosis and AF evoked by ATII. Because it is reported that serum leptin levels were increased in metabolic syndrome subjects, leptin signaling may be a therapeutic target to prevent atrial fibrosis and AF in this population.