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Elevated levels of cardiac mitochondrial uncoupling protein 3 (UCP3) and decreased cardiac efficiency (hydraulic power/oxygen consumption) with abnormal cardiac function occur in obese, diabetic mice. To determine whether cardiac mitochondrial uncoupling occurs in non-genetic obesity, we fed rats a high fat diet (55% kcal from fat) or standard laboratory(More)
BACKGROUND T1 mapping allows direct in-vivo quantitation of microscopic changes in the myocardium, providing new diagnostic insights into cardiac disease. Existing methods require long breath holds that are demanding for many cardiac patients. In this work we propose and validate a novel, clinically applicable, pulse sequence for myocardial T1-mapping that(More)
Neuronal glucose uptake was thought to be independent of insulin, being facilitated by glucose transporters GLUT1 and GLUT3, which do not require insulin signaling. However, it is now known that components of the insulin-mediated glucose uptake pathway, including neuronal insulin synthesis and the insulin-dependent glucose transporter GLUT4, are present in(More)
BACKGROUND Carnitine acetyltransferase catalyzes the reversible conversion of acetyl-coenzyme A (CoA) into acetylcarnitine. The aim of this study was to use the metabolic tracer hyperpolarized [2-(13)C]pyruvate with magnetic resonance spectroscopy to determine whether carnitine acetyltransferase facilitates carbohydrate oxidation in the heart. METHODS AND(More)
Hyperpolarized (13)C-labeled substrates directly provide a source of magnetic resonance (MR) signal to observe the substrates' real-time uptake and enzymatic conversion. The aim of this study was to optimize the concentration of hyperpolarized [1-(13)C]pyruvate infused as a metabolic tracer, by observing the mitochondrial conversion of pyruvate to(More)
Ketone bodies are the most energy-efficient fuel and yield more ATP per mole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, low-carbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson's disease.(More)
Short-term consumption of a high-fat diet impairs exercise capacity in both rats and humans, and increases expression of the mitochondrial uncoupling protein, UCP3, in rodent cardiac and skeletal muscle via activation of the transcription factor, peroxisome proliferator-activated receptor α (PPARα). Unlike long-chain fatty acids however, medium-chain fatty(More)
AIMS Hypertrophic cardiomyopathy (HCM) is the commonest cause of sudden cardiac death in the young, with an excess of exercise-related deaths. The HCM sarcomere mutations increase the energy cost of contraction and impaired resting cardiac energetics has been documented by measurement of phosphocreatine/ATP (PCr/ATP) using (31)Phosphorus MR Spectroscopy(More)
PURPOSE In vivo MRS is often characterized by a spectral signal-to-noise ratio (SNR) that varies highly between experiments. A common design for spectroscopic studies is to compare the ratio of two spectral peak amplitudes between groups, e.g. individual PCr/γ-ATP ratios in 31 P-MRS. The uncertainty on this ratio is often neglected. We wished to explore(More)
BACKGROUND Whether the myocardium in nonischemic heart failure experiences oxygen limitation remains a long-standing controversy. We addressed this question in patients with dilated cardiomyopathy (DCM) using a dual approach. First, we tested the changes in myocardial oxygenation between rest and stress states, using oxygenation-sensitive cardiovascular(More)