Carlos Henríquez-Olguín a , 1 , Leila Baghersad Renani b , 1 , Lyne Arab-Ceschia a , Steffen H. Raun a , Aakash Bhatia a , Zhencheng Li a , Jonas R. Knudsen a , Rikard Holmdahl c , Thomas E. Jensen a , ∗
03 April 2019
Redox, Reactive oxygen species, Exercise, High-intensity interval training, HIIE, high-intensity interval exercise, HIIT, high-intensity interval training, HK II, Hexokinase II, SOD2, superoxide dismutase 2, NOX2, NADPH oxidase 2, ncf1*, B10.Q. p47phox mutated, PDH, pyruvate dehydrogenase, RER, respiratory exchange ratio, ROS, reactive oxygen species
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).
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.
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.
Acute HIIE induces transient NOX2 complex activity in vivo in muscle.
Skeletal muscle adaptations to HIIT were impaired in ncf1-deficient mice.
Functional NOX2 is necessary for HIIT-induced increased expression of antioxidants enzymes.
Ncf1-deficient mice lack HIIT-induced mitochondrial adaptations.