Abstract
AimsLeft ventricular hypertrophy is an adaptive response of the heart to chronic mechanical overload and can lead to functional deterioration and heart failure. Changes in cardiac energy metabolism are considered as key to the hypertrophic remodelling process. The concurrence of obesity and hypertrophy has been associated with contractile dysfunction, and this work therefore aimed to investigate the in vivo structural, functional, and metabolic remodelling that occurs in the hypertrophied heart in the setting of a high-fat, high-sucrose, Western diet (WD).Methods and resultsFollowing induction of cardiac hypertrophy through abdominal aortic banding, male Sprague Dawley rats were exposed to either a standard diet or a WD (containing 45% fat and 16% sucrose) for up to 14 weeks. Cardiac structural and functional characteristics were determined by CINE MRI, and in vivo metabolism was investigated using hyperpolarized 13C-labelled pyruvate. Cardiac hypertrophy was observed at all time points, irrespective of dietary manipulation, with no evidence of cardiac dysfunction. Pyruvate dehydrogenase flux was unchanged in the hypertrophied animals at any time point, but increased incorporation of the 13C label into lactate was observed by 9 weeks and maintained at 14 weeks, indicative of enhanced glycolysis.ConclusionHypertrophied hearts revealed little evidence of a switch towards increased glucose oxidation but rather an uncoupling of glycolytic metabolism from glucose oxidation. This was maintained under conditions of dietary stress provided by a WD but, at this compensated phase of hypertrophy, did not result in any contractile dysfunction.
Highlights
Heart failure continues to be a major cause of death in the Western World
In vivo CINE MRI was used to study the extent of structural remodelling in hearts of animals subjected to abdominal aortic banding (AAB) over time
Left ventricular mass (LVM) was markedly augmented in the AAB group compared with its respective control by 4 weeks post surgery (17%) and this increase was maintained over 9 (14%) and 14 weeks (14%), irrespective of dietary manipulation (Figure 3A)
Summary
Heart failure continues to be a major cause of death in the Western World. The prognosis is poor and patient care is often costly. Patients with heart failure often have pre-existing hypertension and hypertrophy, recognized as independent risk factors in the development of heart failure.[1] Left ventricular hypertrophy (LVH), the adaptive response of the heart to chronic overload, is characterized by cellular and structural remodelling,[2] which may underpin the transition from compensated hypertrophy to decompensated heart failure. The hypertrophied heart undergoes significant metabolic remodelling, switching from dependence upon fatty acids for energy provision to reliance on carbohydrates.[4,5] This switch is underpinned by altered expression of key transcription factors including PPARα and PGC1α, which in turn cause decreased expression of the enzymes involved in fatty acid oxidation.[6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
