Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice.
{"title":"Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice.","authors":"Jiani Lu, Zhengshan Tang, Miaomiao Xu, Jianqiang Lu, Fengmei Wang, Xin Ni, Changnan Wang, Bo Yu","doi":"10.1080/13510002.2024.2347139","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study was to investigate whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle <i>Cth</i> knockout (<i>Cth<sup>Δskm</sup></i>) mice.</p><p><strong>Methods: </strong>The <i>Cth</i><sup><i>Δskm</i></sup> mice and littermate <i>Cth-floxed</i> (<i>Cth<sup>f/f</sup></i>) mice were fed with either HFD or chow diet for 13 weeks. Metabolomics and transcriptome analysis were used to assess the impact of CTH deficiency in skeletal muscle.</p><p><strong>Results: </strong>Metabolomics coupled with transcriptome showed that <i>Cth<sup>Δskm</sup></i> mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in <i>Cth<sup>f/f</sup></i> mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. <i>Cth<sup>Δskm</sup></i>+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to <i>Cth<sup>f/f</sup></i>+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in <i>Cth<sup>Δskm</sup></i>+HFD mice. Omics analysis showed differential pathways enriched between <i>Cth<sup>Δskm</sup></i> mice and <i>Cth<sup>f/f</sup></i> mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in <i>Cth<sup>Δskm</sup></i>+HFD mice compared to <i>Cth<sup>f/f</sup></i>+HFD mice.</p><p><strong>Discussion: </strong>Our results indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Redox Report","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/13510002.2024.2347139","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/8 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: The objective of this study was to investigate whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle Cth knockout (CthΔskm) mice.
Methods: The CthΔskm mice and littermate Cth-floxed (Cthf/f) mice were fed with either HFD or chow diet for 13 weeks. Metabolomics and transcriptome analysis were used to assess the impact of CTH deficiency in skeletal muscle.
Results: Metabolomics coupled with transcriptome showed that CthΔskm mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in Cthf/f mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. CthΔskm+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to Cthf/f+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in CthΔskm+HFD mice. Omics analysis showed differential pathways enriched between CthΔskm mice and Cthf/f mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in CthΔskm+HFD mice compared to Cthf/f+HFD mice.
Discussion: Our results indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.
期刊介绍:
Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included.
While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.