IL-6 Linkage to Exercise-Induced Shifts in Lipid-Related Metabolites: A Metabolomics-Based Analysis

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% VO_2max). 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.