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Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome

Polycystic ovarian syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder. Circulating markers of oxidative stress are abnormal in women with PCOS. There is a close relationship between oxidative stress and insulin resistance (IR). However, little information is available about oxidati...

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Autores principales: Yao, Qiyang, Zou, Xin, Liu, Shihe, Wu, Haowen, Shen, Qiyang, Kang, Jihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569700/
https://www.ncbi.nlm.nih.gov/pubmed/36232686
http://dx.doi.org/10.3390/ijms231911384
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author Yao, Qiyang
Zou, Xin
Liu, Shihe
Wu, Haowen
Shen, Qiyang
Kang, Jihong
author_facet Yao, Qiyang
Zou, Xin
Liu, Shihe
Wu, Haowen
Shen, Qiyang
Kang, Jihong
author_sort Yao, Qiyang
collection PubMed
description Polycystic ovarian syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder. Circulating markers of oxidative stress are abnormal in women with PCOS. There is a close relationship between oxidative stress and insulin resistance (IR). However, little information is available about oxidative stress in the skeletal muscles of those affected by PCOS. In this study, PCOS was induced in prepubertal C57BL/6J mice by injection with dehydroepiandrosterone. Oxidative stress biomarkers were then measured in both serum and skeletal muscles. The underlying mechanisms were investigated in C2C12 myotubes treated with testosterone (T). We discovered increased oxidative biomarkers, increased ROS production, and damaged insulin sensitivity in the skeletal muscles of mice with PCOS. High levels of T caused mitochondrial dysfunction and increased ROS levels through the androgen receptor (AR)-nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) signaling pathway in C2C12 cells. Treatment of C2C12 cells with an antioxidant N-acetylcysteine (NAC) decreased T-induced ROS production, improved mitochondrial function, and reversed IR. Administration of NAC to mice with PCOS improved insulin sensitivity in the skeletal muscles of the animals. Hyperandrogenism caused mitochondrial dysfunction and redox imbalance in the skeletal muscles of mice with PCOS. We discovered that oxidative stress contributed to skeletal muscle IR in PCOS. Reducing ROS levels may improve the insulin sensitivity of skeletal muscles in patients with PCOS.
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spelling pubmed-95697002022-10-17 Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome Yao, Qiyang Zou, Xin Liu, Shihe Wu, Haowen Shen, Qiyang Kang, Jihong Int J Mol Sci Article Polycystic ovarian syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder. Circulating markers of oxidative stress are abnormal in women with PCOS. There is a close relationship between oxidative stress and insulin resistance (IR). However, little information is available about oxidative stress in the skeletal muscles of those affected by PCOS. In this study, PCOS was induced in prepubertal C57BL/6J mice by injection with dehydroepiandrosterone. Oxidative stress biomarkers were then measured in both serum and skeletal muscles. The underlying mechanisms were investigated in C2C12 myotubes treated with testosterone (T). We discovered increased oxidative biomarkers, increased ROS production, and damaged insulin sensitivity in the skeletal muscles of mice with PCOS. High levels of T caused mitochondrial dysfunction and increased ROS levels through the androgen receptor (AR)-nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) signaling pathway in C2C12 cells. Treatment of C2C12 cells with an antioxidant N-acetylcysteine (NAC) decreased T-induced ROS production, improved mitochondrial function, and reversed IR. Administration of NAC to mice with PCOS improved insulin sensitivity in the skeletal muscles of the animals. Hyperandrogenism caused mitochondrial dysfunction and redox imbalance in the skeletal muscles of mice with PCOS. We discovered that oxidative stress contributed to skeletal muscle IR in PCOS. Reducing ROS levels may improve the insulin sensitivity of skeletal muscles in patients with PCOS. MDPI 2022-09-27 /pmc/articles/PMC9569700/ /pubmed/36232686 http://dx.doi.org/10.3390/ijms231911384 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yao, Qiyang
Zou, Xin
Liu, Shihe
Wu, Haowen
Shen, Qiyang
Kang, Jihong
Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome
title Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome
title_full Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome
title_fullStr Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome
title_full_unstemmed Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome
title_short Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome
title_sort oxidative stress as a contributor to insulin resistance in the skeletal muscles of mice with polycystic ovary syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569700/
https://www.ncbi.nlm.nih.gov/pubmed/36232686
http://dx.doi.org/10.3390/ijms231911384
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