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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

Sfyri, Pagona Panagiota; Yuldasheva, Nadira Y.; Tzimou, Anastasia; Giallourou, Natasa; Crispi, Vassili; Aburima, Ahmed; Beltran-Alvarez, Pedro; Patel, Ketan; Mougios, Vassilis; Swann, Jonathan R.; Kearney, Mark T.; Matsakas, Antonios

Authors

Pagona Panagiota Sfyri

Nadira Y. Yuldasheva

Anastasia Tzimou

Natasa Giallourou

Vassili Crispi

Ahmed Aburima

Ketan Patel

Vassilis Mougios

Jonathan R. Swann

Mark T. Kearney

Antonios Matsakas



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.

Journal Article Type Article
Publication Date Dec 1, 2018
Journal Free Radical Biology and Medicine
Print ISSN 0891-5849
Electronic ISSN 1873-4596
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 129
Pages 504-519
APA6 Citation Sfyri, P. P., Yuldasheva, N. Y., Tzimou, A., Giallourou, N., Crispi, V., Aburima, A., …Matsakas, A. (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 & medicine, 129, 504-519. https://doi.org/10.1016...eeradbiomed.2018.10.422
DOI https://doi.org/10.1016/j.freeradbiomed.2018.10.422
Keywords Physiology (medical); Biochemistry
Publisher URL https://www.sciencedirect.com/science/article/pii/S0891584918321932?via%3Dihub

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Copyright Statement
© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/





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