Polystyrene nano-plastics impede skeletal muscle development and induce lipid accumulation via the PPARγ/LXRβ pathway in vivo and in vitro in mice

IF 4.8 2区 医学 Q1 TOXICOLOGY
Ran Xu, Jing-wen Cao, Yuan Geng, Tian-chao Xu, Meng-yao Guo
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Abstract

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRβ pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 μg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRβ as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRβ, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRβ pathway thereby influencing skeletal muscle development.

Abstract Image

聚苯乙烯纳米塑料通过 PPARγ/LXRβ 途径阻碍小鼠体内和体外骨骼肌发育并诱导脂质积累
纳米塑料(NPs)已成为一种重要的环境污染物,广泛存在于水环境中,并随着动物的摄入而对健康和安全构成严重威胁。骨骼肌是复杂生命活动和功能需求的重要器官,但人们对 NPs 影响的关注却很有限。本研究通过给小鼠口服不同大小(1 毫克/千克)的 PS-NPs 研究了聚苯乙烯 NPs(PS-NPs)对骨骼肌发育的影响。研究结果表明,PS-NPs 会导致骨骼肌损伤,并显著阻碍肌肉分化,且与 PS-NPs 颗粒大小呈反相关。形态学分析表明,PS-NPs 造成部分肌肉纤维断裂、纤维间距增大和脂质堆积。RT-qPCR 和 Western 印迹分析表明,暴露于 PS-NPs 会下调肌分化相关因子(Myod、Myog 和 Myh2)的表达,激活 PPARγ/LXRβ 通路,并上调脂质分化相关因子(SREBP1C、SCD-1、FAS、ACC1、CD36/FAT、ADIPOQ、C/EBPα 和 UCP-1)的表达。在体外实验中,使用 C2C12 细胞确认 PS-NPs(0、100、200、400 μg/mL)穿透细胞膜并激活 PPARγ 的表达。此外,为了验证 LXRβ 是一个关键的信号分子,还进行了沉默 RNA 转染实验,结果发现即使暴露于 PS-NPs 后,PPARγ、LXRβ、SREBP1C、FAS、CD36/FAT、ADIPOQ、C/EBPα 和 UCP-1 的表达量也没有增加。然而,SCD-1 和 ACC1 的表达仍然不受影响。本研究证明,暴露于 PS-NPs 会通过 PPARγ/LXRβ 途径诱导脂质积累,从而影响骨骼肌的发育。
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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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