Western diet increases cardiac ceramide content in healthy and hypertrophied hearts.
BACKGROUND AND AIMS
Obesity and cardiac left ventricular hypertrophy (LVH) are recognised independent risk factors in the development of heart failure (HF). However, the combination of these factors may exacerbate the onset of cardiovascular disease by mechanisms as yet unclear. LVH leads to significant cellular remodelling, including alterations in metabolism which may result in an inappropriate accumulation of lipids and eventual lipotoxicity and apoptosis. The aim of the study was to determine the impact of dietary manipulation on cardiac metabolism in the obese and hypertrophied heart.


METHODS AND RESULTS
LVH was induced via aortic constriction (AC) in an experimental model of cardiac hypertrophy and animals subjected to 9 weeks of dietary manipulation with either a standard, high fat, or a sucrose containing Western-style diet (SD, HFD and WD, respectively). This latter diet resulted in accelerated weight gain in both LVH/AC and control animals. LVH was greater in AC animals fed a WD, and both control and AC animals from this diet showed a significant reduction in cardiac fatty acid oxidation and increased triacylglycerol content. Ceramide content was significantly increased in the WD groups, with no additional effect of LVH. Comparison with a model of HF induced by exposure to Doxorubicin and WD showed exacerbated remodelling of cardiac ceramide species leading to increased C16 and C18 content.


CONCLUSIONS
These findings highlight the inappropriate accumulation and re-distribution of cardiac ceramide species in a diet-induced model of obesity and LVH, potentially increasing susceptibility to cell death. The combination of increased fat and sugar leads to greater pathological remodelling and may explain why this diet pattern is consistently linked with poor cardiovascular outcomes.
['Butler|T J|TJ|', 'Ashford|D|D|', 'Seymour|A-M|AM|']
D000818:Animals D002518:Ceramides D059305:Diet, High-Fat D066273:Diet, Western D019422:Dietary Sucrose D004195:Disease Models, Animal D004317:Doxorubicin D005227:Fatty Acids D006333:Heart Failure D017379:Hypertrophy, Left Ventricular D008297:Male D009206:Myocardium D009765:Obesity D010084:Oxidation-Reduction D017207:Rats, Sprague-Dawley D013997:Time Factors D014280:Triglycerides D015854:Up-Regulation
Western diet Ceramide Heart failure Cardiac hypertrophy Sugar High fat diet