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 af dette arbejde

August Krogh Sektionen for Molekylær Fysiologi

50 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Artikelnummer	4623
Tidsskrift	Nature Communications
Vol/bind	10
Antal sider	11
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-019-12523-9
Status	Udgivet - 1 dec. 2019

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10.1038/s41467-019-12523-9Licens: CC BY

Henriquez-Olguin et al_Nature Communications_2019_Vol 10_e4623Forlagets udgivne version, 5,11 MBLicens: CC BY

Citationsformater

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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.",

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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

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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

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