Serum Metabolic Signatures Induced By a Three-Day Intensified Exercise Period Persist After 14 h of Recovery in Runners

Abstract

This study investigated changes in the human serum metabolome elicited by a 3-day period of intensified training. Runners (N = 15, mean ± SD age, 35.2 ± 8.7 years) ran for 2.5 h/day on treadmills at ∼70% VO2max for 3 days in a row, with blood samples collected pre-exercise, and immediately and 14 h post-exercise. Samples were analyzed using gas and liquid chromatography/mass spectrometry (GC-MS, LC-MS), with compounds identified based on comparison to more than 2800 purified standards. Repeated measures ANOVA was used to identify metabolites that differed significantly across time, with multiple testing corrected by the false discovery rate (FDR) (q-value). Immediately following the 3-day exercise period, significant 2-fold or higher increases in 75 metabolites were measured, with all but 22 of these metabolites related to lipid/carnitine metabolism, 13 to amino acid/peptide metabolism, 4 to hemoglobin/porphyrin metabolism, and 3 to Krebs cycle intermediates (q-values < 0.001). After a 14 h overnight recovery period, 50 of the 75 metabolites remained elevated, with 8 decreased (primarily amino acid-related metabolites) (q-values < 0.05). Among the top 20 metabolites, the mean fold changes were 12.4 ± 5.3 and 2.9 ± 1.3 immediately and 14-h post-exercise, respectively. Significant decreases (40-70%, q < 0.01) in 22 metabolites (primarily related to lysolipid and bile acid metabolism) were measured post-exercise, with all but 4 of these still decreased after 14 h rest recovery (q < 0.025). Runners experienced a profound systemic shift in blood metabolites related to energy production especially from the lipid super pathway following 3 days of heavy exertion that was not fully restored to pre-exercise levels after 14 h recovery.

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

“…These results are very similar to those of our previous metabolomicsbased investigation of 15 runners who ran 2.5 h/day at 70% V O 2max 3 days in a row (20). Together, these two studies indicate that following prolonged and intensive exercise, endurance athletes experience profound systemic shifts in blood metabolites, especially those from the lipid pathway.…”

“…After log transformation and imputation with minimum observed values for each compound, repeated measures ANOVA contrasts identified significant Essential FA (7) Ketones (2) Dicarboxylate FA (7) Long chain FA (20) Medium chain FA (4) Fold Change post-75 km cycling time effects for 221 metabolites. Fold changes were calculated from the median scaled intensity values for pre-to-post-75-km cycling time points and then rank ordered.…”

“…We recently reported that a 3-day period of intensified training elicited large changes in the human serum metabolome of runners (20). Athletes ran for 2.5 h/day on treadmills at ϳ70% V O 2max for 3 days in a row, with blood samples collected preexercise and immediately and 14 h postexercise.…”

“…Little information has been published on the influence of exercise on plasma 13-HODE ϩ 9-HODE, and whether postexercise increases relate to changes in established biomarkers of oxidative stress and inflammation (19,20). Using a metabolomics approach, we recently reported that plasma 13-HODE ϩ 9-HODE increased 5.5-fold in 15 runners following a 3-day period of intensified training (2.5 h/day running at 70% V O 2max ), with levels returning to preexercise levels after 14-h recovery (20).…”

“…Using a metabolomics approach, we recently reported that plasma 13-HODE ϩ 9-HODE increased 5.5-fold in 15 runners following a 3-day period of intensified training (2.5 h/day running at 70% V O 2max ), with levels returning to preexercise levels after 14-h recovery (20). Metabolomics allows the simultaneous measurement of hundreds of metabolites and is especially valuable when focusing on complex interactions within the body during exercise or nutrition interventions.…”