Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise

Carlos Henríquez-Olguin; Jonas Roland Knudsen; Steffen Henning Raun; Zhencheng Li; Emilie Dalbram; Jonas Thue Treebak; Lykke Sylow; Rikard Holmdahl; Erik Richter; Enrique Jaimovich; Thomas Elbenhardt Jensen

doi:10.1038/s41467-019-12523-9

Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise

Carlos Henríquez-Olguin, Jonas Roland Knudsen, Steffen Henning Raun, Zhencheng Li, Emilie Dalbram, Jonas Thue Treebak, Lykke Sylow, Rikard Holmdahl, Erik Richter, Enrique Jaimovich, Thomas Elbenhardt Jensen^*

^*Corresponding author for this work

The August Krogh Section for Molecular Physiology

50 Citations (Scopus)

16 Downloads (Pure)

Abstract

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.

Original language	English
Article number	4623
Journal	Nature Communications
Volume	10
Number of pages	11
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-019-12523-9
Publication status	Published - 1 Dec 2019

Keywords

Faculty of Science
Reactive oxygen species (ROS)
Skeletal muscle
GLUT4
NADPH oxidase 2 (NOX2)
Glucose transport
Exercise

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Henriquez-Olguin et al_Nature Communications_2019_Vol 10_e4623Final published version, 5.11 MBLicence: CC BY

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title = "Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise",

abstract = "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.",

keywords = "Faculty of Science, Reactive oxygen species (ROS), Skeletal muscle, GLUT4, NADPH oxidase 2 (NOX2), Glucose transport, Exercise",

author = "Carlos Henr{\'i}quez-Olguin and Knudsen, {Jonas Roland} and Raun, {Steffen Henning} and Zhencheng Li and Emilie Dalbram and Treebak, {Jonas Thue} and Lykke Sylow and Rikard Holmdahl and Erik Richter and Enrique Jaimovich and Jensen, {Thomas Elbenhardt}",

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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

AU - Jaimovich, Enrique

AU - Jensen, Thomas Elbenhardt

N1 - CURIS 2019 NEXS 336

PY - 2019/12/1

Y1 - 2019/12/1

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

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

M1 - 4623

ER -

Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise

Abstract

Keywords

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