In a recent study published in Cell Reports Medicine, researchers in China have advanced understanding of how interactions between epicardial adipose tissue (EAT) and sympathetic neurons contribute to cardiac arrhythmias. Using an in vitro co-culture system of adipocytes, cardiomyocytes, and sympathetic neurons, the team demonstrated how the adipose-neural axis influences arrhythmogenesis. Cardiac arrhythmias, often caused by electrical and structural abnormalities, can result from genetic or acquired heart diseases. Both sympathetic neurons and EAT have been linked to arrhythmia; however, this study explored their combined effect, finding that leptin, a hormone secreted by EAT, activates sympathetic neurons to release neuropeptide Y. This neuropeptide, binding to the Y1 receptor on cardiomyocytes, disrupts calcium ion signaling, potentially through calcium/calmodulin-dependent protein kinase II (CaMKII) and sodium/calcium exchangers, leading to irregular heart rhythms.
The study used stem cell-derived cardiomyocytes, adipocytes, and sympathetic neurons to overcome the challenges of human tissue scarcity and established co-culture models to closely simulate these cellular interactions. Ultrastructural and immunofluorescence analyses revealed that cardiomyocytes in the EAT-sympathetic neuron co-culture exhibited electrical abnormalities, an arrhythmic phenotype, and disrupted calcium signaling. Interestingly, leptin alone did not affect cardiac rhythms unless it was present with sympathetic neurons, and treatment with leptin-neutralizing antibodies or inhibitors of Y1 receptors, Na2+/Ca2+ exchangers, or CaMKII partially mitigated the arrhythmic effects.
These findings suggest that leptin’s interaction with sympathetic neurons plays a crucial role in EAT-related arrhythmias. This research deepens understanding of how adipose and neural elements contribute to heart arrhythmias, highlighting potential therapeutic targets to mitigate the arrhythmic effects linked to epicardial adipose tissue and sympathetic neuron interactions.
