Metabolic signatures of exercise in human plasma

Gregory D. Lewis, Laurie Farrell, Malissa J. Wood, Maryann Martinovic, Zoltan Arany, Glenn C. Rowe, Amanda Souza, Susan Cheng, Elizabeth L. McCabe, Elaine Yang, Xu Shi, Rahul Deo, Frederick P. Roth, Aarti Asnani, Eugene P. Rhee, David M. Systrom, Marc J. Semigran, Ramachandran S. Vasan, Steven A. Carr, Thomas J. WangMarc S. Sabatine, Clary B. Clish, Robert E. Gerszten

Research output: Contribution to journalArticle

228 Scopus citations

Abstract

Exercise provides numerous salutary effects, but our understanding of how these occur is limited. To gain a clearer picture of exercise-induced metabolic responses, we have developed comprehensive plasma metabolite signatures by using mass spectrometry to measure >200 metabolites before and after exercise. We identified plasma indicators of glycogenolysis (glucose-6-phosphate), tricarboxylic acid cycle span 2 expansion (succinate, malate, and fumarate), and lipolysis (glycerol), as well as modulators of insulin sensitivity (niacinamide) and fatty acid oxidation (pantothenic acid). Metabolites that were highly correlated with fitness parameters were found in subjects undergoing acute exercise testing and marathon running and in 302 subjects from a longitudinal cohort study. Exercise-induced increases in glycerol were strongly related to fitness levels in normal individuals and were attenuated in subjects with myocardial ischemia. A combination of metabolites that increased in plasma in response to exercise (glycerol, niacinamide, glucose-6-phosphate, pantothenate, and succinate) up-regulated the expression of nur77, a transcriptional regulator of glucose utilization and lipid metabolism genes in skeletal muscle in vitro. Plasma metabolic profiles obtained during exercise provide signatures of exercise performance and cardiovascular disease susceptibility, in addition to highlighting molecular pathways that may modulate the salutary effects of exercise.

Original languageEnglish (US)
Article number33ra37
JournalScience translational medicine
Volume2
Issue number33
DOIs
StatePublished - May 26 2010

ASJC Scopus subject areas

  • Medicine(all)

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    Lewis, G. D., Farrell, L., Wood, M. J., Martinovic, M., Arany, Z., Rowe, G. C., Souza, A., Cheng, S., McCabe, E. L., Yang, E., Shi, X., Deo, R., Roth, F. P., Asnani, A., Rhee, E. P., Systrom, D. M., Semigran, M. J., Vasan, R. S., Carr, S. A., ... Gerszten, R. E. (2010). Metabolic signatures of exercise in human plasma. Science translational medicine, 2(33), [33ra37]. https://doi.org/10.1126/scitranslmed.3001006