Sfyri, PP, Yuldasheva, NY orcid.org/0000-0001-6213-6358, Tzimou, A et al. (9 more authors) (2018) Attenuation of oxidative stress-induced lesions in skeletal muscle in a mouse model of obesity-independent hyperlipidaemia and atherosclerosis through the inhibition of Nox2 activity. Free Radical Biology and Medicine, 129. pp. 504-519. ISSN 0891-5849
Abstract
Obesity leading to hyperlipidaemia and atherosclerosis is recognised to induce morphological and metabolic changes in many tissues. However, hyperlipidaemia can occur in the absence of obesity. The impact of the latter scenario on skeletal muscle and liver is not understood sufficiently. In this regard, we used the Apolipoprotein E-deficient (ApoE-/-) mouse model, an established model of hyperlipidaemia and atherosclerosis, that does not become obese when subjected to a high-fat diet, to determine the impact of Western-type diet (WD) and ApoE deficiency on skeletal muscle morphological, metabolic and biochemical properties. To establish the potential of therapeutic targets, we further examined the impact of Nox2 pharmacological inhibition on skeletal muscle redox biology. We found ectopic lipid accumulation in skeletal muscle and the liver, and altered skeletal muscle morphology and intramuscular triacylglycerol fatty acid composition. WD and ApoE deficiency had a detrimental impact in muscle metabolome, followed by perturbed gene expression for fatty acid uptake and oxidation. Importantly, there was enhanced oxidative stress in the skeletal muscle and development of liver steatosis, inflammation and oxidative protein modifications. Pharmacological inhibition of Nox2 decreased reactive oxygen species production and protein oxidative modifications in the muscle of ApoE-/- mice subjected to a Western-type diet. This study provides key evidence to better understand the pathophysiology of skeletal muscle in the context of hyperlipidaemia and atherosclerosis and identifies Nox2 as a potential target for attenuating oxidative stress in skeletal muscle in a mouse model of obesity-independent hyperlipidaemia.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2018, Elsevier Inc. All rights reserved. This is an author produced version of a paper published in Free Radical Biology and Medicine. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Atherosclerosis; Western-type diet; NADPH oxidase; Skeletal muscle; Oxidative stress |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) |
Depositing User: | Symplectic Publications |
Date Deposited: | 13 Nov 2018 12:43 |
Last Modified: | 17 Oct 2019 00:39 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.freeradbiomed.2018.10.422 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:138302 |