AUTHOR=Zhong Baiyin , Xie Zhonghui , Zhang Jianhong , Xie Xing , Xie Yuankang , Xie Binhui , Wang Jing , Liu Chuanbin 

TITLE=Identification of key genes increasing susceptibility to atrial fibrillation in nonalcoholic fatty liver disease and the potential mechanisms: mitochondrial dysfunction and systemic inflammation

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1360974

DOI=10.3389/fphar.2024.1360974

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are major health burdens, with emerging evidence suggesting NAFLD as a significant risk factor for AF, but the mechanism is remain unclear.</p><p><bold>Methods:</bold> In this study, we analyzed gene expression data from NAFLD (GSE89632) and AF (GSE75092) datasets from the Gene Expression Omnibus. We identified co-upregulated and co-downregulated genes between NAFLD and AF, assessed diagnostic potential of specific genes, conducted immune infiltration analysis, and performed molecular docking studies with sodium glucose co-transporter 2 inhibitors (SGLT2i).</p><p><bold>Results:</bold> We identified eight co-upregulated and 31 co-downregulated genes between NAFLD and AF. Genes such as <italic>AMOT</italic>, <italic>PDE11A</italic>, <italic>TYMS</italic>, <italic>TMEM98</italic>, and <italic>PTGS2</italic> demonstrated substantial diagnostic potential for identifying NAFLD patients at risk of AF. Immune infiltration analysis discovered an elevated presence of CD8 T cells, γδ T cells, and M2 macrophages in NAFLD livers, linking systemic inflammation to NAFLD and AF. Additionally, studies have shown that a connection between mitochondrial dysfunction and several hub genes like <italic>DGAT1</italic>, <italic>TYMS</italic>, and <italic>PTGS2</italic>, suggesting that mitochondrial disturbances may underpin the systemic inflammation in NAFLD, which possibly exacerbating AF. Molecular docking studies indicated that empagliflozin's binding affinity with key genes such as <italic>DGAT1</italic>, <italic>TYMS</italic>, and <italic>PTGS2</italic> presents a novel therapeutic avenue for NAFLD-associated AF.</p><p><bold>Conclusion:</bold> Our study firstly discovered that <italic>AMOT, PDE11A, TYMS, TMEM98</italic>, and <italic>PTGS2</italic> are associated with NAFLD-related AF and hold strong diagnostic values. Our study also indicates that mitochondrial dysfunction and systemic inflammation may be potential mechanisms bridging NAFLD and AF. Additionally, we identified empagliflozin as a potentially effective therapeutic agent for NAFLD-related AF at the molecular structure level. These novel insights contribute to the further understanding, diagnosis, and intervention of NAFLD-related AF.</p>