Abstract 19448: Altered Cardiomyocyte Glycolysis Causes Cardiac Hypertrophy and Mitochondrial Dysfunction

Introduction: The failing heart is characterized by high rates of glycolysis and low rates of fatty acid oxidation, whereas the diabetic heart shows an opposite cardiac metabotype; however, the role of metabolic changes on myocardial health and mitochondrial function is unclear. Hypothesis: We tested whether metabolic changes that partially phenocopy those occurring in the failing and diabetic heart are sufficient to cause mitochondrial dysfunction and cardiac hypertrophy. Methods/Results: We determined how polarizing cardiac metabolism towards glucose or fat utilization affects cardiac phenotype. Mice expressing cardiac-specific dominant-negative (GlycoLO) phosphofructokinase 2, which decreases glycolytic rate, showed remarkably lower levels of acylcarnitines and fatty acids; conversely, GlycoHI hearts having high glycolytic rates demonstrated increased levels of numerous acylcarnitine species and higher levels of phospholipids compared with WT littermates (A). Both transgenic models displayed hypertroph...