Article pubs.acs.org/jpr
Serum Metabolic Signatures Induced By a Three-Day Intensified Exercise Period Persist After 14 h of Recovery in Runners David C. Nieman,*,‡ R. Andrew Shanely,‡ Nicholas D. Gillitt,† Kirk L. Pappan,§ and Mary Ann Lila# ‡
Human Performance Laboratory, Appalachian State University, North Carolina Research Campus, Kannapolis, North Carolina, United States † Dole Nutrition Research Laboratory, North Carolina Research Campus, Kannapolis, North Carolina, United States § Metabolon, Inc., Durham, North Carolina, United States # Plants for Human Health Institute, North Carolina State University, North Carolina Research Campus, Kannapolis, North Carolina, United States S Supporting Information *
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. KEYWORDS: metabolomics, running, lipids, amino acids, carnitines
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INTRODUCTION Heavy exertion has a profound effect on human metabolism. Until recently, most exercise-related studies have focused on a small, targeted number of biochemicals. The development of metabolite profiling technologies has allowed investigators to obtain a system-wide view of the metabolic response to exercise by simultaneously measuring and identifying a large number of small molecules (
