Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice.

IF 5.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Redox Report Pub Date : 2024-12-01 Epub Date: 2024-05-08 DOI:10.1080/13510002.2024.2347139
Jiani Lu, Zhengshan Tang, Miaomiao Xu, Jianqiang Lu, Fengmei Wang, Xin Ni, Changnan Wang, Bo Yu
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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.

小鼠骨骼肌胱硫醚γ-赖氨酸酶缺乏症会促进肥胖和胰岛素抵抗,并导致高血糖和骨骼肌损伤。
研究目的本研究的目的是利用骨骼肌Cth基因敲除(CthΔskm)小鼠研究骨骼肌胱硫醚γ-赖氨酸(CTH)是否会导致高脂饮食(HFD)诱导的代谢紊乱:方法:将CthΔskm小鼠和同窝Cth-floxed(Cthf/f)小鼠用高脂饮食或低脂饮食喂养13周。代谢组学和转录组分析用于评估CTH缺乏对骨骼肌的影响:代谢组学和转录组显示,CthΔskm小鼠的骨骼肌能量代谢和一些与胰岛素抵抗(IR)相关的信号通路受损,但小鼠的胰岛素敏感性正常。高氟日粮导致 Cthf/f 小鼠骨骼肌中 CTH 表达减少和能量代谢受损。CTH缺乏和HFD在氨基酸代谢、碳代谢和脂肪酸代谢方面有一些共同的富集途径。与Cthf/f+HFD小鼠相比,CthΔskm+HFD小鼠的体重增加、空腹血糖、血浆胰岛素和IR增加,骨骼肌中葡萄糖转运体4和CD36的表达减少。CthΔskm+HFD 小鼠的线粒体受损,肌丝排列不规则。Omics分析表明,CthΔskm小鼠和Cthf/f小鼠在高密度脂蛋白膳食中富集了不同的通路。与 Cthf/f+HFD 小鼠相比,CthΔskm+HFD 小鼠的能量代谢受损、AMPK 信号传导减少、氧化应激和铁蛋白沉积增加的情况更为严重:讨论:我们的研究结果表明,骨骼肌CTH表达失调是高密度脂蛋白胆固醇代谢紊乱的原因之一。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Redox Report
Redox Report 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
28
审稿时长
>12 weeks
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.
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