Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance
Journal article
Xirouchaki, Chrysovalantou E., Jia, Yaoyao, McGrath, Meagan J., Greatorex, Spencer, Tran, Melanie, Merry, Troy L., Hong, Dawn, Eramo, Matthew J., Broome, Sophie C., Woodhead, Jonathan S. T., D'souza, Randall F., Gallagher, Jenny, Salimova, Ekaterina, Huang, Cheng, Schittenhelm, Ralf B., Sadoshima, Junichi, Watt, Matthew J., Mitchell, Christina A. and Tiganis, Tony. (2021). Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance. Science Advances. 7(51), p. Article eabl4988. https://doi.org/10.1126/sciadv.abl4988
Authors | Xirouchaki, Chrysovalantou E., Jia, Yaoyao, McGrath, Meagan J., Greatorex, Spencer, Tran, Melanie, Merry, Troy L., Hong, Dawn, Eramo, Matthew J., Broome, Sophie C., Woodhead, Jonathan S. T., D'souza, Randall F., Gallagher, Jenny, Salimova, Ekaterina, Huang, Cheng, Schittenhelm, Ralf B., Sadoshima, Junichi, Watt, Matthew J., Mitchell, Christina A. and Tiganis, Tony |
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Abstract | Reactive oxygen species (ROS) generated during exercise are considered integral for the health-promoting effects of exercise. However, the precise mechanisms by which exercise and ROS promote metabolic health remain unclear. Here, we demonstrate that skeletal muscle NADPH oxidase 4 (NOX4), which is induced after exercise, facilitates ROS-mediated adaptive responses that promote muscle function, maintain redox balance, and prevent the development of insulin resistance. Conversely, reductions in skeletal muscle NOX4 in aging and obesity contribute to the development of insulin resistance. NOX4 deletion in skeletal muscle compromised exercise capacity and antioxidant defense and promoted oxidative stress and insulin resistance in aging and obesity. The abrogated adaptive mechanisms, oxidative stress, and insulin resistance could be corrected by deleting the H2O2-detoxifying enzyme GPX-1 or by treating mice with an agonist of NFE2L2, the master regulator of antioxidant defense. These findings causally link NOX4-derived ROS in skeletal muscle with adaptive responses that promote muscle function and insulin sensitivity. |
Year | 2021 |
Journal | Science Advances |
Journal citation | 7 (51), p. Article eabl4988 |
Publisher | American Association for the Advancement of Science |
ISSN | 2375-2548 |
Digital Object Identifier (DOI) | https://doi.org/10.1126/sciadv.abl4988 |
PubMed ID | 34910515 |
Scopus EID | 2-s2.0-85121999594 |
PubMed Central ID | PMC8673768 |
Open access | Published as ‘gold’ (paid) open access |
Page range | 1-24 |
Funder | National Health and Medical Research Council (NHMRC) |
Diabetes Australia | |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 15 Dec 2021 |
Publication process dates | |
Accepted | 26 Oct 2021 |
Deposited | 17 Jan 2023 |
Grant ID | APP1162798 |
APP1082253 |
https://acuresearchbank.acu.edu.au/item/8y9v1/skeletal-muscle-nox4-is-required-for-adaptive-responses-that-prevent-insulin-resistance
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Publisher's version
OA_Xirouchaki_2021_Skeletal_muscle_NOX4_is_required_for.pdf | |
License: CC BY-NC 4.0 | |
File access level: Open |
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