Human Skeletal Muscle Lipid Mediator Responses to Resistance Exercise and Anti-inflammatory Drugs

Abstract

Listen

Translate article

Exercise has been found to induce bioactive lipid mediators which possess both pro- and anti-inflammatory activity, yet the role of these mediators in the muscle adaptive response to resistance exercise (RE) remains to be explored. PURPOSE: The present study aimed to characterize the presence of polyunsaturated fatty acid-related bioactive lipids in human skeletal muscle. Specifically, we hypothesized that high doses of anti-inflammatory drugs (NSAIDs) would hinder the action of both pro-inflammatory and pro-resolving lipid mediators in response to acute RE, thereby providing a mechanistic link to the negative effect of high (compared with low) doses of NSAIDs on the muscle hypertrophic response to RE reported by us. METHODS: Thirty-one men and women (18-35 years old) performed 8 weeks of RE with daily consumption of either a high dose of ibuprofen (IBU; 1200 mg) or a low dose of aspirin (ASA; 75 mg). Muscle biopsies were obtained before the training/treatment period and 3 h after an acute RE bout at week 4 of the intervention. We used a targeted lipidomics approach (High-Performance Liquid Chromatography with Tandem Mass Spectrometry) to compare the response of over 140 pro- and anti-inflammatory lipid mediators in IBU and ASA as well as in relation to untreated controls (CON). RESULTS: We could reliably detect 71 lipid metabolites in skeletal muscle, where 12/71 belonged to the cyclooxygenase pathway but the majority of the mediators were from the lipoxygenase and epoxygenase pathways. Overall, both the pro-inflammatory and the pro-resolving lipid mediator signature was decreased in both IBU and ASA, yet remained unchanged with exercise in CON. Pathway analysis revealed significant differences between drug treatments in the lipoxygenase pathway, specifically in mediators derived from the 5-LOX and 15-LOX enzymes, where levels after exercise were significantly lower in ASA compared with IBU. Specific metabolites driving these differences were 5-HETE, 13-OxoODE and 17-HDoHE. CONCLUSIONS: The results show that both high and low doses of NSAIDs markedly affect the skeletal muscle lipid mediator response to RE. We put forth the idea that lipid mediators from the lipoxygenase pathway may have a role in explaining the differential muscle hypertrophic response to RE noted with different doses of NSAID treatment.