Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling.
Bioactive oxidized linoleic acid metabolites (OXLAMs) include 13- and 9-hydroxy-octadecadienoic acid (13-HODE + 9-HODE) and have been linked to oxidative stress, inflammation, and numerous pathological and physiological states. The purpose of this study was to measure changes in plasma 13-HODE + 9-HODE following a 75-km cycling bout and identify potential linkages to linoleate metabolism and established biomarkers of oxidative stress (F2-isoprostanes) and inflammation (cytokines) using a metabolomics approach. Trained male cyclists (N = 19, age 38.0 ± 1.6 yr, wattsmax 304 ± 10.5) engaged in a 75-km cycling time trial on their own bicycles using electromagnetically braked cycling ergometers (2.71 ± 0.07 h). Blood samples were collected preexercise, immediately post-, 1.5 h post-, and 21 h postexercise, and analyzed for plasma cytokines (IL-6, IL-8, IL-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, granulocyte colony-stimulating factor), F2-isoprostanes, and shifts in metabolites using global metabolomics procedures with gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS). 13-HODE + 9-HODE increased 3.1-fold and 1.7-fold immediately post- and 1.5 h postexercise (both P < 0.001) and returned to preexercise levels by 21-h postexercise. Post-75-km cycling plasma levels of 13-HODE + 9-HODE were not significantly correlated with increases in plasma cytokines but were positively correlated with postexercise F2-isoprostanes (r = 0.75, P < 0.001), linoleate (r = 0.54, P = 0.016), arachidate (r = 0.77, P < 0.001), 12,13-dihydroxy-9Z-octadecenoate (12,13-DiHOME) (r = 0.60, P = 0.006), dihomo-linolenate (r = 0.57, P = 0.011), and adrenate (r = 0.56, P = 0.013). These findings indicate that prolonged and intensive exercise caused a transient, 3.1-fold increase in the stable linoleic acid oxidation product 13-HODE + 9-HODE and was related to increases in F2-isoprostanes, linoleate, and fatty acids in the linoleate conversion pathway. These data support the use of 13-HODE + 9-HODE as an oxidative stress biomarker in acute exercise investigations.
Appalachian State University, Human Performance Lab, North Carolina Research Campus, Kannapolis, North Carolina; niemandc@appstate.edu.
David C
DC
Nieman
Appalachian State University, Human Performance Lab, North Carolina Research Campus, Kannapolis, North Carolina;
R Andrew
RA
Shanely
Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China; and.
Beibei
B
Luo
Appalachian State University, Human Performance Lab, North Carolina Research Campus, Kannapolis, North Carolina;
Mary Pat
MP
Meaney
Appalachian State University, Human Performance Lab, North Carolina Research Campus, Kannapolis, North Carolina;
Dustin A
DA
Dew
Metabolon Inc., Durham, North Carolina.
Kirk L
KL
Pappan
D000328:Adult; D001642:Bicycling; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000097:blood; D004734:Energy Metabolism; D028441:F2-Isoprostanes / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008041:Linoleic Acids / Q000097:blood*; D044243:Linoleic Acids, Conjugated / Q000097:blood*; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D005082:Physical Exertion; D053719:Tandem Mass Spectrometry; D013997:Time Factors
D015415:Biomarkers; D016207:Cytokines; D028441:F2-Isoprostanes; D018836:Inflammation Mediators; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; C024347:9-hydroxy-10,12-octadecadienoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid
exercise; inflammation; linoleate; metabolites; oxidative stress