Obesity is a significant global health concern, with rates of obesity rising drastically over the past 50 years. It has been reported that 1.9 billion adults aged over 18 years and 41 million children under the age of 5 years were considered to be overweight or obese in 2016. Obese people are significantly more likely to develop cardiovascular diseases, particularly, arrhythmias such as atrial fibrillation. The mechanism by which obesity leads to an increase in arrhythmia incidence remains unknown. This study used a rat model of diet-induced obesity to investigate mechanisms linking obesity to arrhythmia incidence and susceptibility. Animals were fed a 45% high fat diet (HFD) or a control 10% fat diet for 24 weeks. HFD animals became obese and developed moderate hypertension over the study period but no diabetic phenotype was induced. Recordings of the electrocardiogram in the anaesthetised animal showed that HFD animals had a shortened QRS interval, prolonged QT and QTc intervals and a trend towards an increased incidence of atrial ectopic beats. Langendorff-perfused heart experiments showed that HFD animals were more susceptible to atrial pacing-induced arrhythmias than control animals. In addition, HFD animals had a slower intrinsic heart rate which significantly correlated to body weight. qPCR showed that there were alterations in the expression of a number of genes in the sinoatrial node, and right and left atria of HFD animals including ion channel, calcium handling and connexin genes. Western blot studies showed that there was a significant decrease of calsequestrin 2, Cx40 and Cx43 expression in the right atrium of HFD animals. These changes may be responsible for the increased susceptibility to atrial pacing-induced arrhythmias and the slower intrinsic heart rate observed in HFD animals. In conclusion, this study has shown that diet-induced obesity is associated with significant electrical remodelling of the atria and sinoatrial node which may be responsible for the increased susceptibility to atrial arrhythmias.
|Date of Award||1 Aug 2019|
- The University of Manchester
|Supervisor||Henggui Zhang (Supervisor), Mark Boyett (Supervisor) & Oliver Monfredi (Supervisor)|