Systemic metabolite kinetics mirror skeletal muscle energy metabolism during acute aerobic exercise

Acute exercise increases energy demand in skeletal muscle and releases metabolic intermediates into circulation, yet the serum kinetics of exercise-mobilized metabolites remain poorly characterized. By applying high-frequency serial blood sampling and targeted metabolomics in a longitudinal exercise trial with 12 young, healthy adults (6 females, 6 males), we assessed temporal alterations in energy-related metabolites during acute aerobic exercise and after 1 h of recovery. We provide evidence for 42 exercise-responsive metabolites, including end products of glycolysis, tricarboxylic acid cycle intermediates, ketone bodies, and amino acids. Overall, the observed metabolic alterations closely resembled skeletal muscle energy metabolism, thereby refining fundamental principles of exercise biochemistry through detailed serum kinetics, including novel, so far uncharacterized responses in systemic energy homeostasis and interorgan crosstalk.<b>NEW & NOTEWORTHY</b> In our study, we provide detailed serum kinetics of energy-related metabolites during acute aerobic exercise and after 1 h of recovery. Semantic interpretation of our results against the backdrop of fundamental principles of exercise biochemistry indicate that serum metabolites mirror skeletal muscle energy metabolism, thus providing new insights into systemic energy homeostasis and interorgan crosstalk.