Abstract 13920: Temporal Changes in Metabolism and Gene Expression in Murine Heart Following Exercise

Abstract

Introduction: Previous studies report that many systemic adaptations occur early in an exercise training program, but how exercise leads to cardiac adaptations remain unclear. In this study, we characterized time-dependent changes in cardiac metabolism and gene expression following an acute session of aerobic exercise. Methods: We used untargeted metabolomics to identify the temporal nature of metabolic changes in male and female mouse hearts after an acute bout of forced treadmill running. We freeze-clamped hearts immediately, 1 h, or 24 h following exercise to compare alongside sedentary controls. Additionally, we measured the expression of key metabolic enzymes known to influence cardiac growth via qRT-PCR and immunoblotting. Results: Untargeted metabolomics analyses of male and female mouse hearts ( n =9/gp) revealed exercise-induced changes in branched chain amino acids as well as pentose phosphate, nucleotide, and Krebs cycle intermediates. In both male and female hearts, exercise acutely increased the abundances of corticosterone and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which could indicate a transient role in exercise-induced signaling. AICAR is known to activate AMPK, but immunoblots showed minimal changes in cardiac AMPK phosphorylation immediately after exercise. However, when measured 24 h following an acute bout of exercise, we saw a modest increase in phosphorylation (p=0.07, n =3-4/gp) which suggests time-dependent activation after exercise. Phosphorylation of AKT and PFKFB2 were acutely reduced in the heart following exercise (p<0.05, n =3-4/gp), but normalized 1 h post exercise. At these same timepoints, we observed few changes in expression of genes related to the physiological growth program; however, we did observe an increase in Ppargc1a expression 1 h following exercise (p<0.0001, n =3/gp). Conclusions: These findings show that aerobic exercise acutely changes cardiac metabolism, metabolic signaling pathways, and mitochondrial biogenetic capacity following one bout of aerobic exercise. Temporal changes in cardiac metabolism and gene expression could compound with chronic exercise training and facilitate an exercise-adapted phenotype.