title: 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 >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.
authors.affiliation: Cardiology Division and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA. glewis@partners.org
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
authors.forename: Laurie
authors.initials: L
authors.lastname: Farrell
authors.forename: Malissa J
authors.initials: MJ
authors.lastname: Wood
authors.forename: Maryann
authors.initials: M
authors.lastname: Martinovic
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Arany
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Rowe
authors.forename: Amanda
authors.initials: A
authors.lastname: Souza
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: McCabe
authors.forename: Elaine
authors.initials: E
authors.lastname: Yang
authors.forename: Xu
authors.initials: X
authors.lastname: Shi
authors.forename: Rahul
authors.initials: R
authors.lastname: Deo
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Roth
authors.forename: Aarti
authors.initials: A
authors.lastname: Asnani
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Rhee
authors.forename: David M
authors.initials: DM
authors.lastname: Systrom
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Steven A
authors.initials: SA
authors.lastname: Carr
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001769:Blood / Q000378:metabolism*; D002460:Cell Line; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology
chemical_list: C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1