Abstract
Lipid mediators including classical arachidonic acid‐derived eicosanoids (e.g. prostaglandins and leukotrienes) and more recently identified specialized pro‐resolving‐mediator metabolites of the omega‐3 fatty acids play essential roles in initiation, self‐limitation, and active resolution of acute inflammatory responses. In this study, we examined the bioactive lipid mediator profile of human skeletal muscle at rest and following acute resistance exercise. Twelve male subjects completed a single bout of maximal isokinetic unilateral knee extension exercise and muscle biopsies were taken from the m.vastus lateralis before and at 2, 4, and 24 h of recovery. Muscle tissue lipid mediator profile was analyzed via liquid chromatography–mass spectrometry (LC‐MS)‐based targeted lipidomics. At 2 h postexercise, there was an increased intramuscular abundance of cyclooxygenase (COX)‐derived thromboxanes (TXB 2: 3.33 fold) and prostaglandins (PGE 2: 2.52 fold and PGF 2α: 1.77 fold). Resistance exercise also transiently increased muscle concentrations of lipoxygenase (LOX) pathway‐derived leukotrienes (12‐Oxo LTB 4: 1.49 fold and 20‐COOH LTB 4: 2.91 fold), monohydroxy‐eicosatetraenoic acids (5‐HETE: 2.66 fold, 12‐HETE: 2.83 fold, and 15‐HETE: 1.69 fold) and monohydroxy‐docosahexaenoic acids (4‐HDoHE: 1.69 fold, 7‐HDoHE: 1.58 fold and 14‐HDoHE: 2.35 fold). Furthermore, the abundance of CYP pathway‐derived epoxy‐ and dihydroxy‐eicosatrienoic acids was increased in 2 h postexercise biopsies (5,6‐EpETrE: 2.48 fold, 11,12‐DiHETrE: 1.66 fold and 14,15‐DiHETrE: 2.23 fold). These data reveal a range of bioactive lipid mediators as present within human skeletal muscle tissue and demonstrate that acute resistance exercise transiently stimulates the local production of both proinflammatory eicosanoids and pathway markers in specialized proresolving mediator biosynthesis circuits.
Highlights
Skeletal muscle is a remarkably heterogeneous tissue with the capacity to adapt and respond to external stress
Metabolipidomic profile of human skeletal muscle tissue: Lipid mediator profiles of human skeletal muscle biopsies were generated via targeted liquid chromatography–mass spectrometry (LC-MS)/MS based metabolipidomics
Of the total 125 multiple reaction monitoring (MRM) transitions, 84 unique lipid mediators were reliably detected in resting skeletal muscle tissue
Summary
Skeletal muscle is a remarkably heterogeneous tissue with the capacity to adapt and respond to external stress. Experimental models targeted at manipulating the post-exercise inflammatory response have identified that exercise-induced inflammation is a key regulatory feature in the normal process of tissue regeneration and adaptation following acute muscle damage [25, 32, 57]. This suggests that molecular signaling events occurring early during acute inflammation play an active role in promoting the restoration of normal tissue function and promote skeletal muscle adaptation following an exercise stimulus. The humoral and local muscular changes that occur during exercise-induced inflammation closely resemble that of an acute phase response to cellular stress
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