Abstract 387: Role of Glycolysis in Cardiac Adaptation to Exercise

Abstract

Cardiac stressors affect the function and structure of the heart with prominent effects on metabolism. While the heart typically derives most (~80%) of its energy from fatty acids, the exercised heart is associated with an enhanced capacity to utilize a variety of carbon sources to sustain energy demands that would be advantageous during increased workloads and ischemic events. Due to the central role of glycolysis in glucose metabolism, it is likely that changes in the glycolytic rate regulate cell growth, homeostasis and stress responses. In this study, we assessed how exercise affects glucose metabolism in the myocardium and whether genetically decreasing glycolysis in the heart - using a validated, cardiac-specific, dominant negative form of phosphofructokinase 2 (kd-PFK2) - affects cardiac adaptation to exercise. Adult male FVB/NJ mice were subjected to forced treadmill running for 30 days. Exercise performance was measured and echocardiographic analysis was used to assess changes in cardiac function. Immunoblotting was performed to quantify the abundance of key enzymes involved in glucose metabolism. Exercise training increased exercise capacity by 70% (p < 0.01) and work performed by 69% (p < 0.01). Exercise training also induced cardiac hypertrophy (15%; p < 0.01) associated with a 1.4 fold increase in mitochondrial content (p < 0.05). Cardiac function remained largely unchanged with a significant reduction of 5% in ejection fraction (p < 0.01) and an increase in the left ventricle chamber dimensions (p < 0.05). Relative myocardial abundance of thirteen glycolytic and glucose metabolism enzymes remained unchanged. The kd-PFK2 mice showed that low levels of glycolysis in the heart promote cardiac hypertrophy (15%; p < 0.01) and prevent physiological hypertrophy due to exercise. In comparison with WT mice, the kd-PFK2 mice had a 20% lower exercise capacity (p < 0.05). These findings suggest that the glycolytic rate regulates cardiac adaptations to exercise and may mediate some of the beneficial effects of exercise training on exercise capacity.