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Sci Transl Med DOI:10.1126/scitranslmed.3001006

Metabolic signatures of exercise in human plasma.

Publication TypeJournal Article
Year of Publication2010
AuthorsLewis, GD, Farrell, L, Wood, MJ, Martinovic, M, Arany, Z, Rowe, GC, Souza, A, Cheng, S, McCabe, EL, Yang, E, Shi, X, Deo, R, Roth, FP, Asnani, A, Rhee, EP, Systrom, DM, Semigran, MJ, Vasan, RS, Carr, SA, Wang, TJ, Sabatine, MS, Clish, CB, Gerszten, RE
JournalSci Transl Med
Volume2
Issue33
Pages33ra37
Date Published2010 May 26
ISSN1946-6242
KeywordsAdult, Aged, Animals, Blood, Cell Line, Energy Metabolism, Exercise, Humans, Male, Metabolomics, Mice, Middle Aged, Muscle, Skeletal, Nuclear Receptor Subfamily 4, Group A, Member 1, Psychomotor Performance
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.

URLhttp://stm.sciencemag.org/cgi/pmidlookup?view=long&pmid=20505214
DOI10.1126/scitranslmed.3001006
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/20505214?dopt=Abstract

Alternate JournalSci Transl Med
PubMed ID20505214
PubMed Central IDPMC3010398
Grant ListN01-HC-25195 / HC / NHLBI NIH HHS / United States
R01 HL072872 / HL / NHLBI NIH HHS / United States
R01DK081572 / DK / NIDDK NIH HHS / United States
R01 HL083141 / HL / NHLBI NIH HHS / United States
NS054052 / NS / NINDS NIH HHS / United States
R01 DK081572 / DK / NIDDK NIH HHS / United States
K23HL091106 / HL / NHLBI NIH HHS / United States
P50 HG004233 / HG / NHGRI NIH HHS / United States
K23 HL091106 / HL / NHLBI NIH HHS / United States
U01HL083141 / HL / NHLBI NIH HHS / United States
HG003224 / HG / NHGRI NIH HHS / United States
HG0017115 / HG / NHGRI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 NS054052 / NS / NINDS NIH HHS / United States
HG004233 / HG / NHGRI NIH HHS / United States
K23 HL091106-03 / HL / NHLBI NIH HHS / United States
R01 HG003224 / HG / NHGRI NIH HHS / United States