Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling

Am J Physiol Regul Integr Comp Physiol. 2014 Jul 1;307(1):R68-74. doi: 10.1152/ajpregu.00092.2014. Epub 2014 Apr 23.

Abstract

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.

Keywords: exercise; inflammation; linoleate; metabolites; oxidative stress.

MeSH terms

  • Adult
  • Bicycling*
  • Biomarkers / blood
  • Chromatography, High Pressure Liquid
  • Cytokines / blood
  • Energy Metabolism*
  • F2-Isoprostanes / blood
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Inflammation Mediators / blood
  • Linoleic Acids / blood*
  • Linoleic Acids, Conjugated / blood*
  • Male
  • Metabolomics* / methods
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress
  • Physical Exertion*
  • Tandem Mass Spectrometry
  • Time Factors

Substances

  • Biomarkers
  • Cytokines
  • F2-Isoprostanes
  • Inflammation Mediators
  • Linoleic Acids
  • Linoleic Acids, Conjugated
  • 9-hydroxy-10,12-octadecadienoic acid
  • 13-hydroxy-9,11-octadecadienoic acid