P492Alterations in the myocardial ceramide pool following dietary intervention in an experimental model of cardiac hypertrophy

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Abstract

Purpose

Cardiac remodelling and hypertrophy are known to occur secondary to arterial hypertension. However, the effect of diet upon the hypertrophic remodelling process remains largely unknown. The aim of this study was to determine changes in the ceramide profile of hypertrophied hearts from rats fed either a standard low fat (SD), high-fat (HFD) or "western style" (WD) diet.

Methods

Left ventricular hypertrophy (LVH) was induced surgically in male Sprague-Dawley rats by aortic constriction (AC). Rats were maintained for 9 weeks on an isocaloric diet containing either 7%/5% kcal (SD), 45%/10% kcal (HFD), or 45%/16% kcal fat/sucrose (WD). LVH was assessed from the heart weight/tibia length ratio (HW:TL). At 9 weeks, hearts were excised and ceramides extracted and analysed by LC-MS.

Results

LVH was observed in in all AC groups irrespective of diet (HW:TL: 0.57 ± 0.03 vs. Con + -SD 0.45 ± 0.06 g/cm), (HW:TL 0.55 ± 0.01 vs. Con-HFD 0.49 ± 0.01g/cm) and (0.59 ± 0.02 vs. Con-WD 0.48 ± 0.02). The ratio of medium chain acyl-CoA dehydrogenase (MCAD) to citrate synthase (CS) activities was significantly reduced in the AC-WD group vs.the AC-SD and HFD counterparts (0.13 ± 0.01 vs. 0.23 ± 0.00 and 0.18 ± 0.01 respectively)indicating a down regulation of fatty acid oxidation. Triglyceride (TG) accumulation was observed in both WD groups (2.1 ± 0.1 and 2.4 ± 0.2 µmol/g) compared to the SD groups (1.7 ± 0.2 and 1.6 ± 0.1 µmol/g) and HFD groups (1.5 ± 0.1 and 1.5 ± 0.1 µmol/g). C16:0 ceramide was significantly increased in the AC-WD group compared to their SD and HFD counterparts (54.8 ± 6.2 vs. 2.7 ± 0.5 and 2.1 ± 0.1 ng/g, AC-SD and AC-HFD respectively) with similar findings in the Con-WD group (61.2 ± 6.0 vs. 1.8 ± 0.3 and 2.8 ± 0.5 ng/g, Con-SD and Con-HFD respectively). Total ceramide content was increased in the AC-WD group (1020 ± 166 vs. 189 ± 25 and 112 ± 13 ng/g, AC-SD and AC-HFD respectively) and Con-WD group (1090 ± 130 vs. 124 ± 16 and 115 ± 31 ng/g, Con-SD and Con-HFD respectively).

Discussion

These findings indicate that WD exacerbates cardiac metabolic remodelling in LVH, with a reduction in fatty acid oxidation leading to increases in both the tissue ceramide and triglyceride content which may underpin the onset of lipotoxicity and consequent cardiac dysfunction.

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