Antioxidants Facilitate High-intensity Exercise IL-15 Expression in Skeletal Muscle

Interleukin (IL)-15 stimulates mitochondrial biogenesis, fat oxidation, glucose uptake and myogenesis in skeletal muscle. However, the mechanisms by which exercise triggers IL-15 expression remain to be elucidated in humans. This study aimed at determining whether high-intensity exercise and exercise-induced RONS stimulate IL-15/IL-15R expression and its signaling pathway (STAT3) in human skeletal muscle. Nine volunteers performed a 30-s Wingate test in normoxia and hypoxia (P (I) O (2) =75mmHg), 2h after placebo or antioxidant administration (-lipoic acid, vitamin C and E) in a randomized double-blind design. Blood samples and muscle biopsies ( vastus lateralis ) were obtained before, immediately after, and 30 and 120min post-exercise. Sprint exercise upregulated skeletal muscle IL-15 protein expression (ANOVA, P=0.05), an effect accentuated by antioxidant administration in hypoxia (ANOVA, P=0.022). In antioxidant conditions, the increased IL-15 expression at 120min post-exercise (33%; P=0.017) was associated with the oxygen deficit caused by the sprint (r=-0.54; P=0.020); while, IL-15 and Tyr (705) -STAT3 AUCs were also related (r=0.50; P=0.036). Antioxidant administration promotes IL-15 protein expression in human skeletal muscle after sprint exercise, particularly in severe acute hypoxia. Therefore, during intense muscle contraction, a reduced PO (2) and glycolytic rate, and possibly, an attenuated RONS generation may facilitate IL-15 production, accompanied by STAT3 activation, in a process that does not require AMPK phosphorylation.