PT  - JOURNAL ARTICLE
AU  - Yubao Fan
AU  - Shanshan Huang
AU  - Suhua Li
AU  - Bingyuan Wu
AU  - Li Huang
AU  - Qi Zhao
AU  - Zhenda Zheng
AU  - Xujing Xie
AU  - Jia Liu
AU  - Weijun Huang
AU  - Jiaqi Sun
AU  - Xiulong Zhu
AU  - Maosheng Wang
AU  - Jieming Zhu
AU  - Andy Peng Xiang
AU  - Weiqiang Li
TI  - The adipose-neural axis is critically involved in cardiac arrhythmias
AID  - 10.1101/2022.06.12.495845
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.12.495845
4099  - http://biorxiv.org/content/early/2022/06/13/2022.06.12.495845.short
4100  - http://biorxiv.org/content/early/2022/06/13/2022.06.12.495845.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.