Metabolic signatures of exercise in human plasma.
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.
Lewis
Gregory D
GD
Cardiology Division and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA. glewis@partners.org
Farrell
Laurie
L
Wood
Malissa J
MJ
Martinovic
Maryann
M
Arany
Zoltan
Z
Rowe
Glenn C
GC
Souza
Amanda
A
Cheng
Susan
S
McCabe
Elizabeth L
EL
Yang
Elaine
E
Shi
Xu
X
Deo
Rahul
R
Roth
Frederick P
FP
Asnani
Aarti
A
Rhee
Eugene P
EP
Systrom
David M
DM
Semigran
Marc J
MJ
Vasan
Ramachandran S
RS
Carr
Steven A
SA
Wang
Thomas J
TJ
Sabatine
Marc S
MS
Clish
Clary B
CB
Gerszten
Robert E
RE
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
C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1