TY - JOUR
T1 - Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
AU - Henríquez-Olguin, Carlos
AU - Knudsen, Jonas Roland
AU - Raun, Steffen Henning
AU - Li, Zhencheng
AU - Dalbram, Emilie
AU - Treebak, Jonas Thue
AU - Sylow, Lykke
AU - Holmdahl, Rikard
AU - Richter, Erik A.
AU - Jaimovich, Enrique
AU - Jensen, Thomas Elbenhardt
N1 - CURIS 2019 NEXS 336
PY - 2019
Y1 - 2019
N2 - Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers, mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo, but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source, regulating glucose transport capacity during moderate-intensity exercise.
AB - Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers, mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo, but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source, regulating glucose transport capacity during moderate-intensity exercise.
KW - Faculty of Science
KW - Reactive oxygen species (ROS)
KW - Skeletal muscle
KW - GLUT4
KW - NADPH oxidase 2 (NOX2)
KW - Glucose transport
KW - Exercise
U2 - 10.1038/s41467-019-12523-9
DO - 10.1038/s41467-019-12523-9
M3 - Journal article
C2 - 31604916
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4623
ER -