Abstract
IL-6 and lipolysis have been linked in cell culture and IL-6 infusion studies, but this has not yet been tested using metabolomics-based procedures that allow the simultaneous evaluation of a high number of metabolites from the lipid super pathway following intensive exercise. PURPOSE: Metabolomic profiling and bioinformatic technologies were used to determine the relationship between exercise-induced increases in IL-6 and lipid-related metabolites. METHODS: Male runners (N=24, 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), with vastus lateralis muscle biopsy and blood samples collected before and after the running bout. RESULTS: The runners experienced 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 plasma 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), but did reveal a relationship between changes in serum cortisol and lipid-related metabolites (R2Y=1, Q2Y=0.434). 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. CONCLUSION: This metabolomics-based analysis showed that the substantial increase in lipid metabolites after prolonged and intensive running was related more to changes in cortisol than increases in IL-6 and epinephrine, or muscle glycogen depletion. Taken together, the metabolomics-based data from this study do not support a strong relationship between the modest increase in IL-6 and the large increase in numerous lipid-related metabolites following prolonged and intensive running. Funding: Reoxcyn Discoveries Group, Salt Lake City, UT
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