Diabetes is an independent
risk factor for
atrial fibrillation (AF). This study aimed to elucidate the pathophysiology of diabetes-related AF from the perspective of the gut microbial metabolite trimethylamine N-
oxide (TMAO). In the present study,
male rats received either a normal
diet to serve as the
control group or a
high-fat diet /
streptozotocin to induce
type 2 diabetes mellitus . Then, diabetic
rats were divided into two groups based on the presence or absence of 3,3-dimethyl-
1-butanol (DMB, a specific TMAO inhibitor) in
drinking water the
diabetic cardiomyopathy (DCM) group and the DCM + DMB group. Eight weeks later, compared with control
rats ,
rats in the DCM group exhibited
gut microbiota dysbiosis and systemic TMAO elevation. The inflammatory
cytokines IL-1 β,
IL-6 , and TNF-α were markedly increased in the atria of
rats in the DCM group. Downregulated expression of
connexin 40 and lateralized distribution of
connexin 43 were also observed in the atria of DCM
rats . AF inducibility was significantly higher in DCM
rats than in control
rats . Furthermore, DMB
treatment effectively ameliorated atrial
inflammation and
connexin remodeling while markedly reducing
plasma TMAO levels. DMB
treatment also decreased the
vulnerability of diabetic
rats to AF. In conclusion, TMAO might promote atrial
inflammation and
connexin remodeling in the development of diabetes, which may
play a key
role in
mediating diabetes-related AF. (AU)