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Cardiovascular Research Advance Access originally published online on November 21, 2008
Cardiovascular Research 2009 81(3):610-617; doi:10.1093/cvr/cvn316
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Western diet impairs metabolic remodelling and contractile efficiency in cardiac hypertrophy

Ashwin Akki{dagger} and Anne-Marie L. Seymour*

Department of Biological Sciences, Hull York Medical School, University of Hull, Cottingham Road, Kingston-upon-Hull HU6 7RX, UK

* Corresponding author. Tel: +44 1482 465517; fax: +44 1482 465458. E-mail address: a.m.seymour{at}hull.ac.uk

Aims: Metabolic remodelling in cardiac hypertrophy is underscored by a reduction in fatty acid (FA) oxidation. We tested whether this decline in FA oxidation in the presence of enhanced FA supply may predispose the hypertrophied myocardium to lipid accumulation, functional deterioration, and eventually heart failure.

Methods: and results Left ventricular hypertrophy was induced surgically in Sprague–Dawley rats by inter-renal aortic constriction. Rats were fed a Western diet (WD, 45% kcal from lipids) or standard diet (SD, 12% kcal from fat) for 9 weeks post-surgery. Hearts were perfused in the isovolumic mode with a physiological mixture of substrates including 5 mM 1-13C glucose, 1 mM 3-13C lactate, and 0.3 mM U-13C palmitate, and cardiac function was monitored. Real-time PCR was used to determine transcript levels of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) and PPAR{alpha}-regulated metabolic enzymes. Palmitate oxidation and PPAR{alpha}-regulated gene expression were markedly reduced in the hypertrophied myocardium of rats fed SD. However, 9 weeks of WD normalized both palmitate oxidation and PPAR{alpha}-regulated gene expression but significantly increased glucose and lactate oxidation in the hypertrophied hearts. This was accompanied by cardiac triglyceride accumulation and a decline in ventricular function despite an increase in oxygen consumption.

Conclusion: These results highlight that WD-induced dysregulation of FA metabolism has deleterious functional consequences in cardiac hypertrophy.

KEYWORDS Left ventricular hypertrophy; Western diet; Metabolic remodelling; Lipid metabolism; Real-time PCR


Time for primary review: 26 days

{dagger} Present address. Department of Cardiology, King's College, London School of Medicine, The James Black Centre, 125 Coldharbour Lane, London SE5 9NU, UK.


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