Metabolic Signatures of Exercise in Human Plasma

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 over 200 metabolites before and after exercise. We identified plasma indicators of glycogenolysis (glucose-6-phosphate), tricarboxylic acid (TCA) cycle span 2 expansion (succinate, malate, and * To whom correspondence should be addressed Corresponding authors Robert E. Gerszten, MD Cardiology Division and Center for Immunology & Inflammatory Diseases Massachusetts General Hospital, Room 8307 149 13th Street Charlestown, MA 02129 rgerszten@partners.org Gregory D. Lewis, MD Cardiology Division Massachusetts General Hospital, GRB 800 55 Fruit Street, Boston, MA 02114 glewis@partners.org. Authors contributions: G.D.L conceived the study, designed the experiments, performed primary data analysis and wrote the manuscript. M.J.W. led the effort to recruit and phenotype marathon subjects, L.F. and M.M. recruited subjects, processed samples, and assisted with experimental design. Z.A. and G.C.R. designed and performed the gene expression profiling experiments, A.S., E.Y., X.S., A.A., S.A.C. and C.B.C. developed the metabolic profiling platform, performed mass spectrometry experiments, and analyzed the data, S.C., E.L.M, T.W., and R.S.V. designed experiments and analyzed data from the Framingham Heart Study cohort, R.D. and F.P.R. assisted with statistical analysis and constructed the metabolite interrelatedness dendrogram, E.P.R. contributed to mass spectrometry data analysis and helped to write the manuscript, D.M.S. and M.J.S. contributed to the cardiopulmonary exercise testing metabolic profiling experiment, M.S.S. helped to conceive and design the exercise treadmill testing studies and assisted in data interpretation and in writing the manuscript, R.E.G. conceived of the study, designed experiments, analyzed data, and wrote the manuscript. Competing interests:The authors declare that they have no competing interests. NIH Public Access Author ManuscriptSci Transl Med. Author manuscript; available in PMC 2010 December 27. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 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, 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) upregulated the expression of nur77, a transcriptional regulator of glucose utilization and lipid metabolism genes in skeleta...

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