NADPH-oxidase 2 is required for molecular adaptations to high-intensity interval training in skeletal muscle.

Henriquez-Olguin, C.; Baghersad Renani, L.; Arab-Ceschia, L.; Raun, S. H.; Bhatia, A.; Li, Z.; Knudsen, J. R.; Holmdahl, R.; Jensen, T.

doi:10.1101/542514

bioRxiv · 10.1101/542514

NADPH-oxidase 2 is required for molecular adaptations to high-intensity interval training in skeletal muscle.

Henriquez-Olguin, C.·Baghersad Renani, L.·Arab-Ceschia, L.·Raun, S. H.·Bhatia, A.·Li, Z.·Knudsen, J. R.·Holmdahl, R.·Jensen, T.

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Abstract

Objective: Reactive oxygen species (ROS) have been proposed as signaling molecules mediating exercise training adaptation, but the ROS source has remained unclear. This study aimed to investigate the requirement for NADPH oxidase (NOX)2-dependent redox changes induced by acute and long-term high-intensity interval training (HIIT) in skeletal muscle in a mouse model lacking functional NOX2 complex due to deficient p47phox (Ncf1) subunit expression (ncf1* mutation). Methods: HIIT was investigated after an acute bout of exercise and after a chronic intervention (3x week for 6 weeks) in wildtype (WT) vs. NOX2 activity-deficient (ncf1*) mice. NOX2 activation during HIIT was measured using a genetically-encoded biosensor. Immunoblotting and single-fiber staining were performed to measure classical exercise-training responsive endpoints in skeletal muscle. Results: A single bout of HIIT increased NOX2 activity measured using electroporated p47roGFP oxidation immediately after exercise but not 1h after exercise. After a 6-week of HIIT regime, improvements in maximal running capacity and some muscle training-markers responded less to HIIT in the ncf1* mice compared to WT, including superoxide dismutase (SOD)2, catalase, hexokinase II (HK II), pyruvate dehydrogenase (PDH) and protein markers of mitochondrial oxidative phosphorylation complexes. Strikingly, HIIT-training increased mitochondrial network area and decreased fragmentation in WT mice only. Conclusion: This study provided evidence that HIIT exercise activates NOX2 complex in skeletal muscle and that the presence of functional NOX2 is required for specific skeletal muscle adaptations to HIIT relating to antioxidant defense, glucose metabolism, and mitochondria.

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Henriquez-Olguin, C., Baghersad Renani, L., Arab-Ceschia, L., Raun, S. H., Bhatia, A., Li, Z., Knudsen, J. R., Holmdahl, R., Jensen, T.. 2019-02-06. NADPH-oxidase 2 is required for molecular adaptations to high-intensity interval training in skeletal muscle.. https://doi.org/10.1101/542514

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