Abstract
Technological advances now permit the simultaneous detection of previously unattainable numbers of small molecule metabolic products (the metabolome) in blood. Metabolomics facilitates analysis of dynamic, interacting physiologic systems and unravelling the role of physical activity during the process of growth in disease prevention across the lifespan. PURPOSE: To evaluate the effect of an acute intense bout of exercise on plasma metabolomics in a group of healthy adolescents, and explore sex-related patterns. Methods: 29 normal weight healthy adolescents (14-17 y/o, 16 girls) performed 10, 2-min bouts of cycle ergometer exercise interspersed with 1-min rest at a constant work equivalent to ~75% of their peak V[Combining Dot Above]O2. Blood was collected at baseline and immediately after the exercise. Untargeted profiling of primary metabolism was performed using automatic liner exchange/cold injection GC-TOF mass spectrometry at the UC Davis WCM Center. An acute exercise effect was assessed using paired t test (FDR ≤0.05). Two- way repeated measure ANOVA followed by paired t test was carried out to evaluate sex differences. Pathway analysis was performed using MetaboAnalyst 3 (FDR≤0.05). Results: Exercise caused a significant shift in plasma metabolites associated with major bioenergetics, aerobic, anaerobic and amino acid metabolism. 48 annotated metabolites (36↑12↓) were classified into 11 metabolism pathways (e.g., citrate cycle, alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, arginine and proline metabolism and aminoacyl-tRNA biosynthesis). 11 metabolites had different response to exercise in boys compared to girls. 4 of them were enriched (FDR=0.01) in the arginine and proline metabolism pathway, which plays a role in maintenance of vascular tone and hemodynamics, and acts in muscle metabolism. CONCLUSION: The rapidly emerging field of metabolomics enables us to identify interacting networks of cellular metabolites activated by exercise. Our exploratory data revealed that exercise induced a shift in the metabolic profile indicating global cellular metabolic/energetic stress and sex dimorphism not previously observed. Supported by NIH Grant P01HD-048721 and PERC System Biology Fund
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