Atrial Fibrillation (AF), for which metabolic syndrome is a major risk factor, is associated with severe complications including embolic stroke. A strong consensus supports the involvement of endothelial dysfunction in AF. Brain-derived Neurotrophic Factor (BDNF) is expressed in endothelial cells and its decrease is involved in glucose metabolism reprogramming, a primordial cause of endothelial damage. Moreover, BDNF reduced AF episodes in clinical settings when administered at low doses.

The aim of this study was to characterize the implication of BDNF in the onset of AF in a context of metabolic syndrome.

An original model of metabolic syndrome induced by post-natal overfeeding (PNOF) in C57BL/6 male mice was used. It is based on reducing the litters size shortly after birth. At the age of six months, electrocardiograms were recorded by telemetry, and transesophageal electrophysiological exploration was performed to assess AF inducibility. BDNF mRNA expression and localization in the heart were analyzed at 6- and 12-months using RT-qPCR and immunohistochemistry.

Electrophysiology experiments showed that 4 out of 13 PNOF mice exhibited spontaneous AF episodes and 5 after stimulation, compared to none in the control group. PCR analyzes revealed that BDNF mRNA was more expressed in the left ventricle than in both atria (P<0.001) and its expression was significantly lower in the left atrium of PNOF mice (P<0.01). Immunohistochemistry suggested that BDNF was expressed in cardiomyocytes.

In conclusion, mice with metabolic syndrome induced by PNOF are prone to spontaneous and pacing-evoked AF episodes by six months of age. These findings are associated with transcriptional alterations of BDNF in the left atrium. Our results pave the path for a possible implication of BDNF in the onset of AF in a context of metabolic syndrome. Specific investigation about the possible expression of BDNF in endothelial cells are ongoing.