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Int J Sports Med. 2019 Jan;40(1):16-22. doi: 10.1055/a-0781-2527. Epub 2018 Nov 29.

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

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Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Acalá de Henares, Spain.
Research Institute of Biomedical and Health Sciences (IUIBS), Universidad de Las Palmas de Gran Canaria - Campus de Tafira, Las Palmas de Gran Canaria, Spain.
Department of Physical Education, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
Complejo Hospitalario Universitario Insular-Materno Infantil de Las Palmas de Gran Canaria, Clinical Genetics Unit, Las Palmas de Gran Canaria, Spain.


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-15Rα expression and its signaling pathway (STAT3) in human skeletal muscle. Nine volunteers performed a 30-s Wingate test in normoxia and hypoxia (PIO2=75 mmHg), 2 h after placebo or antioxidant administration (α-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 120 min 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 120 min 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 Tyr705-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 PO2 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.

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