To further explore the influence of the sex-specific metabolites on sex differences in AF, the transcriptomic signature of the left atrium in male patients and female patients with AF compared to those with sinus rhythm (SR) were analyzed, respectively. For male patients, 2205 DEGs were observed between the AF and SR groups under the settings of |log2FC| > 1 and p < 0.05. Among them, 2179 were upregulated DEGs and 26 were downregulated DEGs (Figure 3A). Consistent with the high levels of series of metabolites including amino acids, peptides and their analogs, indoles, fatty acids and their conjugates, and fatty acid esters, GO analysis highlighted that the DEGs of the left atrium in male patients with AF were mainly involved in metabolic process. Mitochondrial-related pathways were represented multiple times, along with the generation of precursor metabolites and energy and the positive regulation of cellular catabolic process (Figure 3B). In comparison, there were 550 DEGs between the AF and SR groups in female patients, of which 508 DEGs were upregulated and 42 DEGs were downregulated in the AF group (Figure 3C). GO analysis showed that the DEGs of the left atrium in female patients were concentratedly involved in the immune response and regulation based on immune cells, cytokines, and chemokines (Figure 3D), which suggested the probable influence of metabolites like Glycerophosphocholine and phosphatidylcholine, which were higher in female patients with AF. And, it is worth noting that only 288 DEGs were commonly regulated in male and female patients when comparing the AF group and SR group. However, there were 1917 DEGs only specifically regulated in male patients and 262 DEGs specifically regulated in female patients (Figure 3E). Considering the significant association between 7-Methylguanosine, succinic acid, and AF, the expression of genes related to the metabolism of them were further compared (Figure 3F). QKI was significantly increased in the left atrium of male patients with AF compared those with SR, which was reported to modulate 7-Methylguanosine modifications in tRNA. The expression of QKI was not significantly altered between the AF and SR groups in female patients. The gene related to the metabolism of succinic acid, SUCLA2, was significantly increased in the left atrium of male patients with AF compared those with SR (fold change = 1.53; p = 0.008), while it had little change in female patients. SUCNR1 was obviously raised in the left atrium of female patients with AF but not in male patients.