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Compensated cardiac hypertrophy is characterised by a decline in palmitate oxidation

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Abstract

Cardiac hypertrophy is an independent risk factor in the development of heart failure. However, the cellular mechanisms underlying the transition from compensated hypertrophy to heart failure are incompletely understood. The aim of this study was to investigate changes in myocardial substrate utilisation and function in pressure-overload hypertrophy (using 13C NMR spectroscopy) in parallel with alterations in the expression pattern of genes involved in cardiac fatty acid and glucose uptake and oxidation. Left ventricular hypertrophy was induced surgically in Sprague–Dawley rats by inter-renal aortic constriction. Nine weeks later, hearts were perfused in the isovolumic mode with a physiological mixture of substrates including 5 mM 1-13C glucose, 1 mM 3-13C lactate, 0.1 mM U-13C pyruvate and 0.3 mM U-13C palmitate and cardiac function monitored simultaneously. Real-time PCR was used to determine mRNA levels of PPARα and PPARα-regulated metabolic enzymes. Results showed that at the stage of compensated hypertrophy, fatty acid oxidation (FAO) and expression of genes involved in FAO were markedly reduced, whilst pyruvate oxidation was enhanced, highlighting the fact that metabolic remodelling is an early event in the development of cardiac hypertrophy.

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Abbreviations

ATP:

Adenosine triphosphate

MCAD:

Medium-chain acyl-CoA dehydrogenase

NMR:

Nuclear magnetic resonance

PCR:

Polymerase chain reaction

PDH:

Pyruvate dehydrogenase

PPARα:

Peroxisome proliferator-activated receptor-α

PGC1:

Peroxisome-proliferator-activated receptor-γ co-activator 1

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Acknowledgements

Ashwin Akki was a recipient of the Graduate Teaching Assistantship from the University of Hull. We thank Mrs. Jenny Foster and Mrs. Kath Bulmer for excellent technical support, Mr. Denys Bilko for technical advice with Real-time PCR and Mr. K.Y. Lee for help with Western blotting. Thanks also go to Dr. Jessica Sample for constructive discussions and critical review of the manuscript.

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Correspondence to Anne-Marie L. Seymour.

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Akki, A., Smith, K. & Seymour, AM.L. Compensated cardiac hypertrophy is characterised by a decline in palmitate oxidation. Mol Cell Biochem 311, 215–224 (2008). https://doi.org/10.1007/s11010-008-9711-y

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