摘要
背景:细胞衰老是一种由有丝分裂和代谢应激触发的稳定生长停滞状态。年龄增长和高脂肪饮食(HFD)已被证明是各种器官衰老的诱因,给全球老龄化人口提出了挑战。我们前期研究发现,ROS净化剂N-乙酰半胱氨酸(NAC)可以改善饮食诱导的肥胖小鼠的胰岛素抵抗(IR)和慢性炎症,早期干预效果更好。在此,我们研究了NAC是否可以改善饮食诱导的肥胖小鼠模型的细胞衰老,以及早期干预是否具有遗留效应。 材料与方法:12个月疗程,C57B/L6小鼠分别饲喂鼠粮(CD)、高脂高糖饲料(HFD)、CD+NAC1-12 (NAC干预1-12月)、HFD+NAC1-12、HFD+NAC1-6 (NAC干预1-6月)。采用静态分析方法分析细胞衰老和炎症的不同标志物。 结果:在整个研究过程中,HFD组表现出体重(BW)和体脂显著增加、衰老标志物、肌肉活动(MA)降低和糖耐量受损。与HFD组相比,HFD+NAC1-12组MA增加,体重和体脂降低,糖耐量改善,衰老标志物降低。HFD+NAC1-6组尽管停用NAC6个月但疗效依然与HFD+NAC1-12组疗效相似。我们的研究表明,NAC显著增加了HFD+NAC1-12和HFD+NAC1-6组的MA,改善了HFD诱导的线粒体和细胞内ROS表达、DNA和蛋白氧化损伤以及脂肪组织炎症。 结论:NAC干预下HFD诱导的细胞衰老确实存在遗留效应,其可能机制为运动活性持续增加和抗氧化应激作用。
关键词: 细胞衰老、肥胖、胰岛素抵抗、2型糖尿病、遗留效应、N -乙酰半胱氨酸。
Current Molecular Medicine
Title:Legacy Effect of Antioxidant N-acetylcysteine in Cellular Senescence of Diet-induced Obesity Mice
Volume: 21 Issue: 6
关键词: 细胞衰老、肥胖、胰岛素抵抗、2型糖尿病、遗留效应、N -乙酰半胱氨酸。
摘要:
Background: Cellular senescence is a state of stable growth arrest triggered by mitogenic and metabolic stressors. Ageing and a high-fat diet (HFD) are proven inducers of senescence in various organs, presenting a challenge for ageing populations worldwide. Our previous study demonstrated that ROS scavenger N-acetylcysteine (NAC) can improve insulin resistance (IR) and chronic inflammation in diet-induced obesity mice, an effect better achieved through early intervention. We, herein, investigate whether NAC can improve cellular senescence in a diet-induced obesity mouse model, and whether a legacy effect is presented with early intervention.
Materials and Methods: For a twelve-month treatment course, all C57B/L6 mice were fed a chow diet (CD), high-fat high-sucrose diet (HFD), CD+NAC1-12 (NAC intervention 1st-12th month), HFD+NAC1-12, and HFD+NAC1-6 (NAC intervention 1st-6th month). Staticalanalysis was used to analyze the different markers of cellular senescence and inflammation.
Results: Throughout the study, the HFD group exhibited significantly increased body weight (BW) and body fat, markers of senescence, decreased motor activity (MA) and impaired glucose tolerance. Compared to the HFD group, the HFD+NAC1-12 group exhibited increased MA, decreased BW and body fat, improved glucose tolerance, and decreased senescence markers.The HFD+NAC1-6 group showed similar effects to the HFD+NAC1-12 group, despite discontinuing NAC for 6 months. Our study showed that NAC significantly increased MA in both HFD+NAC1-12 and HFD+NAC1-6 groups, and improved HFD-induced mitochondrial and intracellular ROS expression, DNA and protein oxidative damage, and adipose tissue inflammation.
Conclusion: Legacy effect was indeed presented in HFD-induced cellular senescence with NAC intervention, with possible mechanisms being persistently increased motor activity and anti-oxidative stress effects.
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Cite this article as:
Legacy Effect of Antioxidant N-acetylcysteine in Cellular Senescence of Diet-induced Obesity Mice, Current Molecular Medicine 2021; 21 (6) . https://dx.doi.org/10.2174/1566524020999201113101738
DOI https://dx.doi.org/10.2174/1566524020999201113101738 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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