title: Alteration of energy substrates and ROS production in diabetic cardiomyopathy.
abstract: Diabetic cardiomyopathy is initiated by alterations in energy substrates. Despite excess of plasma glucose and lipids, the diabetic heart almost exclusively depends on fatty acid degradation. Glycolytic enzymes and transporters are impaired by fatty acid metabolism, leading to accumulation of glucose derivatives. However, fatty acid oxidation yields lower ATP production per mole of oxygen than glucose, causing mitochondrial uncoupling and decreased energy efficiency. In addition, the oxidation of fatty acids can saturate and cause their deposition in the cytosol, where they deviate to induce toxic metabolites or gene expression by nuclear-receptor interaction. Hyperglycemia, the fatty acid oxidation pathway, and the cytosolic storage of fatty acid and glucose/fatty acid derivatives are major inducers of reactive oxygen species. However, the presence of these species can be essential for physiological responses in the diabetic myocardium.
authors.affiliation: IIS-Fundación Jiménez Díaz, Autónoma University, Avenue Reyes Católicos 2, 28040 Madrid, Spain ; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Network, 08017 Barcelona, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Lorenzo
authors.forename: E
authors.initials: E
authors.lastname: Ramírez
authors.forename: B
authors.initials: B
authors.lastname: Picatoste
authors.forename: J
authors.initials: J
authors.lastname: Egido
authors.forename: J
authors.initials: J
authors.lastname: Tuñón
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D058065:Diabetic Cardiomyopathies / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D009206:Myocardium / Q000473:pathology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005227:Fatty Acids; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D004247:DNA; D005947:Glucose; D010100:Oxygen