title: IL-6 Linkage to Exercise-Induced Shifts in Lipid-Related Metabolites: A Metabolomics-Based Analysis.
abstract: Metabolomics profiling and bioinformatics technologies were used to determine the relationship between exercise-induced increases in IL-6 and lipid-related metabolites. Twenty-four male runners (age 36.5 ± 1.8 y) ran on treadmills to exhaustion (2.26 ± 0.01 h, 24.9 ± 1.3 km, 69.7 ± 1.9% VO2max). Vastus lateralis muscle biopsy and blood samples were collected before and immediately after running and showed a 33.7 ± 4.2% decrease in muscle glycogen, 39.0 ± 8.8-, 2.4 ± 0.3-, and 1.4 ± 0.1-fold increases in plasma IL-6, IL-8, and MCP-1, respectively, and 95.0 ± 18.9 and 158 ± 20.6% increases in cortisol and epinephrine, respectively (all, P < 0.001). The metabolomics analysis revealed changes in 209 metabolites, especially long- and medium-chain fatty acids, fatty acid oxidation products (dicarboxylate and monohydroxy fatty acids, acylcarnitines), and ketone bodies. OPLS-DA modeling supported a strong separation in pre- and post-exercise samples (R2Y = 0.964, Q2Y = 0.902). OPLSR analysis failed to produce a viable model for the relationship between IL-6 and all lipid-related metabolites (R2Y = 0.76, Q2Y = -0.0748). Multiple structure equation models were evaluated based on IL-6, with the best-fit pathway model showing a linkage of exercise time to IL-6, then carnitine, and 13-methylmyristic acid (a marker for adipose tissue lipolysis) and sebacate. These metabolomics-based data indicate that the increase in plasma IL-6 after long endurance running has a minor relationship to increases in lipid-related metabolites.
authors.affiliation: Human Performance Laboratory, Appalachian State University , North Carolina Research Campus, Kannapolis, North Carolina 28081, United States.
authors.forename: David C
authors.identifier: 0000-0002-8305-1860
authors.initials: DC
authors.lastname: Nieman
authors.affiliation: Bioinformatics Services Division, University of North Carolina at Charlotte , North Carolina Research Campus, Kannapolis, North Carolina 28081, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.affiliation: Metabolon, Inc. , Durham, North Carolina 27713, United States.
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Pappan
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D002331:Carnitine / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008066:Lipolysis; D008297:Male; D055432:Metabolomics; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D005082:Physical Exertion; D012420:Running / Q000502:physiology*
chemical_list: D005227:Fatty Acids; C508600:IL6 protein, human; D015850:Interleukin-6; D002331:Carnitine; D006854:Hydrocortisone; D004837:Epinephrine
keywords: cortisol; epinephrine; interleukin-6; metabolomics; running