title: Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis.
abstract: Introduction. 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.Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n= 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 Cav1.2, HCN4, Kir2.1, 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 Ca2+transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca2+transient, both of which would be expected to be arrhythmogenic.Conclusion. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules.
authors.affiliation: Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
authors.forename: Reza
authors.identifier: 0000-0002-2397-281X
authors.initials: R
authors.lastname: Ashrafi
authors.affiliation: Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
authors.forename: Marianne
authors.initials: M
authors.lastname: Yon
authors.affiliation: Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Pickavance
authors.affiliation: Institute of Cardiovascular Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Yanni Gerges
authors.affiliation: Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
authors.forename: Gershan
authors.initials: G
authors.lastname: Davis
authors.affiliation: Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
authors.forename: John
authors.initials: J
authors.lastname: Wilding
authors.affiliation: Biological Physics Group, School of Physics & Astronomy, University of Manchester, Schuster Building, Oxford Road, Manchester M13 9PL, UK.
authors.forename: Kun
authors.initials: K
authors.lastname: Jian
authors.affiliation: Biological Physics Group, School of Physics & Astronomy, University of Manchester, Schuster Building, Oxford Road, Manchester M13 9PL, UK.
authors.forename: Henggui
authors.identifier: 0000-0002-0863-5807
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK.
authors.forename: George
authors.initials: G
authors.lastname: Hart
authors.affiliation: Institute of Cardiovascular Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Boyett
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000150:complications / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015220:Calcium Channels; D004041:Dietary Fats