Adaptations to high-intensity interval training in skeletal muscle require NADPH oxidase 2

TY - JOUR

T1 - Adaptations to high-intensity interval training in skeletal muscle require NADPH oxidase 2

AU - Henríquez-Olguín, Carlos

AU - Baghersad Renani, Leila

AU - Arab-Ceschia, Lyne

AU - Raun, Steffen Henning

AU - Bhatia, Aakash

AU - Li, Zhencheng

AU - Knudsen, Jonas Roland

AU - Holmdahl, Rikard

AU - Jensen, Thomas Elbenhardt

N1 - CURIS 2019 NEXS 119 Copyright © 2019. Published by Elsevier B.V.

PY - 2019/6

Y1 - 2019/6

N2 - 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 if increased NADPH oxidase (NOX)2-dependent activity during exercise is required for long-term high-intensity interval training (HIIT) in skeletal muscle using a mouse model lacking functional NOX2 complex due to absent 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 wild-type (WT) vs. NOX2 activity-deficient (ncf1*) mice. NOX2 activation during HIIT was measured using an electroporated genetically-encoded biosensor. Immunoblotting and single-fiber microscopy was performed to measure classical exercise-training responsive endpoints in skeletal muscle.Results: A single bout of HIIT increased NOX2 activity measured as p47-roGFP oxidation immediately after exercise but not 1 h or 4 h after exercise. After a 6-week HIIT regimen, improvements in maximal running capacity and some muscle training-markers responded less to HIIT in the ncf1* mice compared to WT, including superoxide dismutase 2, catalase, hexokinase II, pyruvate dehydrogenase 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 suggests that HIIT exercise increases NOX2 activity in skeletal muscle and shows that NOX2 activity is required for specific skeletal muscle adaptations to HIIT relating to antioxidant defense, glucose metabolism, and mitochondria.

AB - 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 if increased NADPH oxidase (NOX)2-dependent activity during exercise is required for long-term high-intensity interval training (HIIT) in skeletal muscle using a mouse model lacking functional NOX2 complex due to absent 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 wild-type (WT) vs. NOX2 activity-deficient (ncf1*) mice. NOX2 activation during HIIT was measured using an electroporated genetically-encoded biosensor. Immunoblotting and single-fiber microscopy was performed to measure classical exercise-training responsive endpoints in skeletal muscle.Results: A single bout of HIIT increased NOX2 activity measured as p47-roGFP oxidation immediately after exercise but not 1 h or 4 h after exercise. After a 6-week HIIT regimen, improvements in maximal running capacity and some muscle training-markers responded less to HIIT in the ncf1* mice compared to WT, including superoxide dismutase 2, catalase, hexokinase II, pyruvate dehydrogenase 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 suggests that HIIT exercise increases NOX2 activity in skeletal muscle and shows that NOX2 activity is required for specific skeletal muscle adaptations to HIIT relating to antioxidant defense, glucose metabolism, and mitochondria.

KW - Faculty of Science

KW - Redox

KW - Reactive oxygen species

KW - Exercise

KW - High-intensity interval training (HIIT)

U2 - 10.1016/j.redox.2019.101188

DO - 10.1016/j.redox.2019.101188

M3 - Journal article

C2 - 30959461

SN - 2213-2317

VL - 24

JO - Redox Biology

JF - Redox Biology

M1 - 101188

ER -