Am J Physiol Regul Integr Comp Physiol. 2014 Apr 23. [Epub ahead of print]
Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling.
Nieman DC, Shanely RA, Luo B, Meaney MP, Dew DA, Pappan KL.
Appalachian State University Human Performance Laboratory, NC Research Campus.
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 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 y, 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 pre-exercise, and immediately post-, 1.5-h post-, and 21-h post-exercise, and analyzed for plasma cytokines (IL-6, IL-8, IL-10, TNFα, MCP-1, GCSF), F2-isoprostanes, and shifts in metabolites using global metabolomics procedures with GC-MS and LC-MS. 13-HODE + 9-HODE increased 3.1-fold and 1.7-fold immediately post- and 1.5-h post-exercise (both p<0.001), and returned to pre-exercise levels by 21-h post-exercise. 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 post-exercise 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.