Abstract Body: Atrial fibrillation (AF) is characterized by episodes of rapid and irregular heart rate. Obesity increases AF risk. The impact of high fat diet (HFD) on atrial structural and electrical remodeling in the context of AF is not clear. We hypothesized that HFD promotes AF onset and progression. Our goal was to evaluate the impact of HFD on evidence of first AF and heart rate variability in a mouse model of spontaneous onset of AF.

Wild-type (WT) and cAMP responsive element modulator IbΔC-X heterozygous (TG) male and female mice were fed HFD (45 kcal% fat) or matched control diet (CD, 10 kcal% fat) beginning at 4 weeks. AF burden was assessed weekly by electrocardiography (ECG) through 15 weeks.

Terminal body weight was increased (p<0.05) in WT HFD compared to WT CD in females and males but was not altered in TG HFD compared to WT HFD (Fig 1A,B). Left atrial (LA) weight was increased (p<0.0001) in TG CD and TG HFD compared to WT CD and WT HFD in both male and female mice (Fig 1C,D). LA weight was not increased in WT HFD or TG HFD compared to WT CD or TG CD. The coefficient of variation of RR intervals (CVRR), a measure of heart rate variability, was increased at 11 weeks in male TG CD (p<0.0001) and TG HFD (p<0.001) compared to WT CD and WT HFD and was maintained through 15 weeks. In female mice, CVRR was increased at 9 weeks in TG CD (p<0.008) and at 10 weeks in TG HFD (p<0.009) compared to diet controls. ECGs were evaluated to identify the timepoint that AF was first evident. AF was not evident in WT CD males and females (Fig 2A,B). AF was first observed in WT HFD males at 8 weeks and WT HFD females at 14 weeks. In TG males, AF was first evident in CD and HFD at 6 weeks (Fig 2C). Notably, all TG HFD males were in AF by 8 weeks, 2 weeks earlier than TG CD males. In TG females, AF was observed at 6 weeks (Fig 2D). All TG CD and TG HFD females were in AF by 11 weeks.

Our data provide suggestive evidence of earlier AF onset in female WT, male WT, and male TG mice fed HFD. Future studies will extend the duration of HFD, evaluate AF burden, and examine the mechanisms underlying AF susceptibility in the presence of a HFD.