Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis
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 hi...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Obesity |
| Online Access: | http://dx.doi.org/10.1155/2016/7127898 |
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| author | Reza Ashrafi Marianne Yon Lucy Pickavance Joseph Yanni Gerges Gershan Davis John Wilding Kun Jian Henggui Zhang George Hart Mark Boyett |
| author_facet | Reza Ashrafi Marianne Yon Lucy Pickavance Joseph Yanni Gerges Gershan Davis John Wilding Kun Jian Henggui Zhang George Hart Mark Boyett |
| author_sort | Reza Ashrafi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e732b0233ea045aab2aaf92dc199b56e |
| institution | Kabale University |
| issn | 2090-0708 2090-0716 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Obesity |
| spelling | doaj-art-e732b0233ea045aab2aaf92dc199b56e2025-02-03T01:08:49ZengWileyJournal of Obesity2090-07082090-07162016-01-01201610.1155/2016/71278987127898Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced ArrhythmogenesisReza Ashrafi0Marianne Yon1Lucy Pickavance2Joseph Yanni Gerges3Gershan Davis4John Wilding5Kun Jian6Henggui Zhang7George Hart8Mark Boyett9Department 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, UKDepartment 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, UKDepartment 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, UKInstitute of Cardiovascular Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UKDepartment 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, UKDepartment 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, UKBiological Physics Group, School of Physics & Astronomy, University of Manchester, Schuster Building, Oxford Road, Manchester M13 9PL, UKBiological Physics Group, School of Physics & Astronomy, University of Manchester, Schuster Building, Oxford Road, Manchester M13 9PL, UKInstitute of Cardiovascular Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UKInstitute of Cardiovascular Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UKIntroduction. 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.http://dx.doi.org/10.1155/2016/7127898 |
| spellingShingle | Reza Ashrafi Marianne Yon Lucy Pickavance Joseph Yanni Gerges Gershan Davis John Wilding Kun Jian Henggui Zhang George Hart Mark Boyett Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis Journal of Obesity |
| title | Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis |
| title_full | Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis |
| title_fullStr | Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis |
| title_full_unstemmed | Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis |
| title_short | Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis |
| title_sort | altered left ventricular ion channel transcriptome in a high fat fed rat model of obesity insight into obesity induced arrhythmogenesis |
| url | http://dx.doi.org/10.1155/2016/7127898 |
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