RT Journal Article
SR Electronic
T1 Metabolic Signatures of Exercise in Human Plasma
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 33ra37
OP 33ra37
DO 10.1126/scitranslmed.3001006
VO 2
IS 33
A1 Lewis, Gregory D.
A1 Farrell, Laurie
A1 Wood, Malissa J.
A1 Martinovic, Maryann
A1 Arany, Zoltan
A1 Rowe, Glenn C.
A1 Souza, Amanda
A1 Cheng, Susan
A1 McCabe, Elizabeth L.
A1 Yang, Elaine
A1 Shi, Xu
A1 Deo, Rahul
A1 Roth, Frederick P.
A1 Asnani, Aarti
A1 Rhee, Eugene P.
A1 Systrom, David M.
A1 Semigran, Marc J.
A1 Vasan, Ramachandran S.
A1 Carr, Steven A.
A1 Wang, Thomas J.
A1 Sabatine, Marc S.
A1 Clish, Clary B.
A1 Gerszten, Robert E.
YR 2010
UL http://stm.sciencemag.org/content/2/33/33ra37.abstract
AB 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. Copyright © 2010, American Association for the Advancement of Science