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The impact of a high–fat (HF) diet on eccentric left ventricular hypertrophy (LVH) from severe volume overload is still not well understood. The purpose of this study was to investigate the long–term impact of a HF diet on survival, LVH and myocardial metabolism in a model of dilated cardiomyopathy from severe aortic regurgitation (AR) in rats.
Adult male rats underwent AR induction or sham (S) surgery and were fed with control chow (C) or a HF diet (60% fat). Rats were divided into four groups: 1) sham (n=15) fed control diet (SC), 2) sham fed high fat–diet (n=15; SHF), 3) ARC (n=96), and 4) ARHF (n=32).
Survival was significantly decreased in ARHF compared to the ARC group at 7 months (47 vs. 70%; p=0.035). As expected, LV weight was increased in ARC animals compared to SHC (1.8 vs. 1.2g; p<0.0001) and even more in ARHF rats (2.1g; p<0.05). HF diet had no effect both on survival or hypertrophy in sham rats. LVH in AR is associated with an increased glucose uptake and a decrease in the uptake of fatty acids. The activity levels of the 3–hydroxyacyl–CoA dehydrogenase, citrate synthase, carnitine palmitoyltranserase, complex–1, succinate dehydrogenase and the malonyl–CoA carboxylase were decreased in ARC but HF diet reversed this trend associated with eccentric LVH and normalized these activities (all p<0.05 vs. ARC respectively). On the other, activity of hexokinase was deceased in ARHF group (p<0.05 vs. ARC). HF diet increased phosphorylation of AMPK and GSK3β but did the opposite on mTOR and 4E–BP1 (p<0.05 vs. ARC respectively). FAT/CD36 and MCAD gene expression was increased by HF in AR animals (p<0.0001 for both).
Our data show that although HF diet seemingly preserved mitochondrial enzyme activities, it was associated with poorer survival and increased LVH in AR rats. Since the use of fatty acids by the myocardium is associated with increased use of oxygen for ATP production, the impact of the HF diet may decreased cardiac myocyte overall efficiency. Moreover the increased concentrations of fatty acids from the diet may lead to accumulation into the cardiac myocyte cytoplasm and to lipotoxicity which could be responsible for aggravated LVH and mortality.
Poster Sessions, Expo North
Sunday, March 10, 2013, 3:45 p.m.–4:30 p.m.
Session Title: Preclinical and Translational Research
Abstract Category: 49. TCT@ACC–i2: Aortic Valve Disease
Presentation Number: 2111–248
- 2013 American College of Cardiology Foundation