title: Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy.
abstract: Heart disease is a leading cause of death worldwide. In many forms of heart disease, including heart failure, ischaemic heart disease and diabetic cardiomyopathies, changes in cardiac mitochondrial energy metabolism contribute to contractile dysfunction and to a decrease in cardiac efficiency. Specific metabolic changes include a relative increase in cardiac fatty acid oxidation rates and an uncoupling of glycolysis from glucose oxidation. In heart failure, overall mitochondrial oxidative metabolism can be impaired while, in ischaemic heart disease, energy production is impaired due to a limitation of oxygen supply. In both of these conditions, residual mitochondrial fatty acid oxidation dominates over mitochondrial glucose oxidation. In diabetes, the ratio of cardiac fatty acid oxidation to glucose oxidation also increases, although primarily due to an increase in fatty acid oxidation and an inhibition of glucose oxidation. Recent evidence suggests that therapeutically regulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation can improve cardiac function of the ischaemic heart, the failing heart and in diabetic cardiomyopathies. In this article, we review the cardiac mitochondrial energy metabolic changes that occur in these forms of heart disease, what role alterations in mitochondrial fatty acid oxidation have in contributing to cardiac dysfunction and the potential for targeting fatty acid oxidation to treat these forms of heart disease.
authors.affiliation: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Fillmore
authors.forename: J
authors.initials: J
authors.lastname: Mori
authors.forename: G D
authors.initials: GD
authors.lastname: Lopaschuk
mesh_terms: D058065:Diabetic Cardiomyopathies / Q000188:drug therapy / Q000503:physiopathology*; D004734:Energy Metabolism / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D058990:Molecular Targeted Therapy / Q000379:methods*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects
chemical_list: D005227:Fatty Acids
keywords: PPARα; glucose oxidation; malonyl CoA; pyruvate dehydrogenase