The adipose-neural axis is critically involved in cardiac arrhythmias

Fan, Y.; Huang, S.; Li, S.; Wu, B.; Huang, L.; Zhao, Q.; Zheng, Z.; Xie, X.; Liu, J.; Huang, W.; Sun, J.; Zhu, X.; Wang, M.; Zhang, J.; Xiang, A. P.; Li, W. Y.

doi:10.1101/2022.06.12.495845

bioRxiv · 10.1101/2022.06.12.495845

The adipose-neural axis is critically involved in cardiac arrhythmias

Fan, Y.·Huang, S.·Li, S.·Wu, B.·Huang, L.·Zhao, Q.·Zheng, Z.·Xie, X.·Liu, J.·Huang, W.·Sun, J.·Zhu, X.·Wang, M.·Zhang, J.·Xiang, A. P.·Li, W. Y.

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Abstract

Dysfunction of the sympathetic nervous system and increase of epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive due to a lack of appropriate human disease models. Here, using the in vitro co-culture system with sympathetic neurons, cardiomyocytes, and adipocytes, we show that adipocyte-derived leptin could activate sympathetic neurons and increase the release of NPY, which in turn trigger arrhythmia of cardiomyocytes by interaction with NPY1R and subsequently enhancing the activity of NCX and CaMKII. The arrhythmic phenotype could be partially blocked by leptin neutralizing antibody, or an inhibitor of NPY1R, NCX or CaMKII. More importantly, increased EAT thickness accompanied with higher leptin/NPY blood levels was detected in atrial fibrillation patients compared to control group. Our study provides the first evidence that adipose-neural axis would contribute to arrhythmogenesis and represent a potential therapeutic target for arrhythmia.

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Fan, Y., Huang, S., Li, S., Wu, B., Huang, L., Zhao, Q., Zheng, Z., Xie, X., Liu, J., Huang, W., Sun, J., Zhu, X., Wang, M., Zhang, J., Xiang, A. P., Li, W. Y.. 2022-06-13. The adipose-neural axis is critically involved in cardiac arrhythmias. https://doi.org/10.1101/2022.06.12.495845

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