title: Compensated cardiac hypertrophy is characterised by a decline in palmitate oxidation.
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 PPARalpha and PPARalpha-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.
authors.affiliation: Department of Biological Sciences, University of Hull, Cottingham Road, Kingston-upon-Hull HU6 7RX, UK.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Akki
authors.forename: Katie
authors.initials: K
authors.lastname: Smith
authors.forename: Anne-Marie L
authors.initials: AM
authors.lastname: Seymour
mesh_terms: D000818:Animals; D001011:Aorta / Q000033:anatomy & histology / Q000473:pathology / Q000601:surgery; D004734:Energy Metabolism / Q000235:genetics; D005786:Gene Expression Regulation; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000503:physiopathology; D008928:Mitochondria / Q000201:enzymology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D010168:Palmitates / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010168:Palmitates