Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA013

Poster Communications

High-fat diet causes arrhythmogenic remodelling of the atria and sinus node

K. Webb1, S. Logantha1, M. Absi1, E. J. Cartwright1, H. Zhang1, O. Monfredi1, M. R. Boyett1

1. Cardiovascular, University of Manchester, Merseyside, United Kingdom.


Obesity is a significant global health concern. It increases the risk of developing a variety of cardiovascular diseases, particularly atrial fibrillation (AF). Population studies have shown that increases in body mass index are associated with a parallel increase in AF risk (1). However, the mechanisms which link obesity to arrhythmias are poorly defined. Male Sprague-Dawley rats were fed either a control diet of 10% fat (n=24) or a high fat diet (HFD) of 45% fat (n=24) for 24 weeks. Animals fed a HFD weighed 24% more than control animals at the end of the study period (631±11 vs 780±16 g; n=24, P<0.0001, ANOVA). Langendorff-perfused isolated heart experiments showed that effective refractory periods in the atrioventricular node (107.4±8 ms, n=8 vs. 60.7±11 ms, n=9; P<0.01, Student's t-test) and ventricle (52.3±4.5 ms, n=6 vs. 37.3±2, n=6; P<0.05, Student's t-test) were shorter in HFD fed animals. HFD fed animals had a slower intrinsic heart rate (209±8 beats/min, n=10 vs. 177±8 beats/min, n=10; P<0.05, Student's t-test), which was significantly correlated to body weight (P=0.002; R2=0.4, Pearson's correlation coefficient). Most importantly, animals fed a HFD were more susceptible to atrial S1/S2 pacing-induced arrhythmias (3/8 control animals vs. 8/9 HFD animals; P<0.05, Chi-squared test) and showed a similar trend towards more ventricular S1/S2 pacing-induced arrhythmias (0/8 control animals vs. 3/8 HFD animals; P=0.06, Chi-squared-test). qPCR using Taqman microfluidic cards showed that of 44 genes investigated (including ion channel, Ca2+-handling and connexin genes), there were significant alterations of 41%, 46% and 32% in the left and right atria and sinus node, respectively, in HFD animals. Data were analysed using RealTime Statminer software; statistical significance was tested using a non-parametric limma test and the Benjamini-Hochberg FDR with FDR-corrected P<0.2. Pro-arrhythmic changes included significant downregulation of; calsequestrin and phospholamban in the right atrium (3.7 ± 0.25; n=9 vs. 1.1 ± 0.05; n=8 and 4 ± 0.29; n=9 vs. 3 ± 0.13; n=8), connexin 40 in the left and right atria (0.009 ± 0.002; n=7 vs. 0.003 ± 0.0005; n=6 and 0.0038 ± 0.0004; n=9 vs. 0.0027 ± 0.0003; n=8), and Kv4.2 (0.036 ± 0.005; n=7 vs. 0.024 ± 0.002, n=6) in the left atrium. Further, there was upregulation of KvLQT1 (0.057 ± 0.0027; n=11 vs. 0.067 ± 0.0025; n=12), TASK1 (0.17 ± 0.014; n=11 vs. 0.23 ± 0.019; n=12) and Kir2.1 (0.011 ± 0.00058; n=11 vs. 0.014 ± 0.00056; n=12) in the sinus node which may contribute to the intrinsic bradycardia observed in HFD animals. These data show that a HFD causes a variety of electrophysiological changes, including significant remodelling of key ion channel, connexin and Ca2+-handling genes, which may underlie the increased susceptibility to atrial arrhythmias.

Where applicable, experiments conform with Society ethical requirements