Exposure to a chronic high-fat diet promotes atrial structure and gap junction remodeling in rats.

Abstract

Obesity has been demonstrated to be linked to atrial fibrillation(AF) with atrial enlargement and tissue fibrosis. Long-term high calorie intake is the main reason for the prevalence of obesity. To investigate the possible causes of AF, such as chronic high-fat diet(HFD), and to identify the underlying mechanisms, the present study analyzed a variety of structural and gap junctional electrophysiological alterations in the atria of female rats fed an HFD. After consistent HFD feeding of female rats for 12weeks, hematoxylin and eosin(H&E) and Masson's staining, RT-qPCR, western blotting, immunofluorescence and TUNEL staining were performed. In our study, approximately 3/5 of the HFD-fed rats (HFD-OB, n=13) displayed a significant increase in body weight, while the other 2/5 did not (HFD-NOB, n=8). In addition, the atrial weight of the HFD-OB and HFD-NOB rats was markedly heavier, as compared to the rats fed a normal diet(CT,n=20). According to the plasma lipid levels, both HFD-OB andHFD-NOB rats exhibited dyslipidemia. Furthermore, H&E staining revealed broadened interstitial space and myocyte disarray in atria of the HFD-fed rats (i.e.,HFD-OB and HFD-NOB rats). Expression levels of atrial fibrosis relevant factors, transforming growth factor-β1 and matrix metalloproteinase-2, were significantly upregulated in the HFD-fed rat atria. In addition, we found a gap junction remodeling with distinct alterations in expression and distribution of connexin 40(Cx40) andCx43 in the HFD-fed rat atria. Moreover, a modest increase in apoptotic cell death in both the HFD-OB and HFD-NOB rat atria was detected. Taken together, our findings demonstrated that the impact of chronic HFD on atria displayed in the diet-induced obese rats was observed in HFD-fed rats in the absence of obesity as well.