Abstract

Introduction Obesity is a common risk factor for atrial fibrillation (AF). The precise mechanisms by which obesity promotes AF, are not fully understood. Furthermore, the interaction between obesity induced electrical and structural remodelling and genetic pre-disposition for AF, remains unexplored. Mutations in the vicinity of the paired like homeodomain-2 transcription factor (PITX2) gene have been associated with the increased risk of AF development. Aim Investigate how high fat diet (HFD) and PITX2c isoform deficiency alters left atrial electrophysiology. Methods Wild type (WT) and pitx2c+/- male and female mice were fed a high fat "SDS Western" diet (HFD) for 20 weeks, Simultaneously, age-matched mice were fed on a control diet. Following the diet, the left atria was dissected, and optical mapping was performed using transmembrane voltage dye DI-4-ANEPPS to assess electrophysiology. Atria were paced at cycle lengths of 120, 100 and 80 ms, and raw data was analysed using ElectroMap. Results HFD increased body weight to 48.6±1.5 g versus 40.0±1.8 g for WT animals on control diet (P=0.0032). Similarly, pitx2null mice fed on HFD had a body weight of 47.0±1.3 g versus 35.5±1.3 g (P = 0.0004) for control diet. Action potential duration to 80% was prolonged by HFD when compared to control conditions (26.1±1.4 vs 20.04±2.7 ms; P=<0.0001) in WT mice (figures 1 and 2). Similarly, HFD prolonged APD80 of pitx2null mice (19.5±2.3 vs 16.26±2.1 ms; P=0.02) (figures 1 and 2). Pitx2null mice exhibited shorter APD80 than WT mice on the same diet, however these differences were not significant. Conduction velocity was not significantly altered by HFD or genotype. Conclusion High fat diet alters left atrial electrophysiology, independent of Pitx2 expression. Conflict of Interest n/a