Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis.



Ashrafi, Reza ORCID: 0000-0002-2397-281X, Yon, Marianne, Pickavance, Lucy, Yanni Gerges, Joseph, Davis, Gershan, Wilding, John, Jian, Kun, Zhang, Henggui ORCID: 0000-0002-0863-5807, Hart, George and Boyett, Mark
(2016) Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis. Journal of obesity, 2016. 7127898 - ?.

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Abstract

<i>Introduction</i>. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. <i>Methods and Results</i>. Rats were fed on a high-fat diet and compared to control rats on a normal diet (<i>n</i> = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR. Obese rats had significant upregulation of Ca<sub>v</sub>1.2, HCN4, K<sub>ir</sub>2.1, RYR2, NCX1, SERCA2a, and RYR2 mRNA and downregulation of ERG mRNA. In the case of HCN4, it was confirmed that there was a significant increase in protein expression. The potential effects of the mRNA changes on the ventricular action potential and intracellular Ca<sup>2+</sup> transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca<sup>2+</sup> transient, both of which would be expected to be arrhythmogenic. <i>Conclusion</i>. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules.

Item Type: Article
Uncontrolled Keywords: Heart Ventricles, Animals, Rats, Rats, Wistar, Obesity, Dietary Fats, Calcium Channels, Polymerase Chain Reaction, Gene Expression Regulation, Male, Arrhythmias, Cardiac
Depositing User: Symplectic Admin
Date Deposited: 16 Apr 2018 09:42
Last Modified: 20 Jul 2022 22:10
DOI: 10.1155/2016/7127898
URI: https://livrepository.liverpool.ac.uk/id/eprint/3020127