Jan Kucera, Zuzana Chalupova, Martin Wabitsch, Julie Bienertova-Vasku
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In this study, we screened human exposure-relevant doses of various EDCs on the SGBS cell line to investigate their effects on viability, lipid accumulation and adipogenesis-related protein expression. Submicromolar doses were generally well tolerated; however, at higher doses, EDCs compromised cell viability, with cadmium chloride (CdCl<sub>2</sub>) showing the most pronounced effects. Intracellular lipid levels remained unaffected by EDCs, except for tributyltin (TBT), used as a positive control, which induced a significant increase. Analysis of adipogenesis-related protein expression revealed several effects, including downregulation of fatty acid-binding protein 4 (FABP4) by dibutyl phthalate, upregulation by CdCl<sub>2</sub> and downregulation of perilipin 1 and FABP4 by perfluorooctanoic acid. Additionally, TBT induced dose-dependent upregulation of C/EBPα, perilipin 1 and FABP4 protein expression. These findings underscore the importance of employing appropriate models to study EDC-adipocyte interactions. 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引用次数: 0
摘要
工业化学品的使用日益增多,引起了人们对暴露于干扰内分泌的化学品(EDCs)的关注,这些化学品会干扰发育、生殖和新陈代谢过程。尤其令人担忧的是它们与脂肪组织之间的相互作用,而脂肪组织是内分泌系统中调节代谢和荷尔蒙功能的重要组成部分。SGBS(辛普森-戈拉比-贝梅尔综合征)细胞系是一种成熟的人体脂肪细胞研究相关模型,它密切模拟原生脂肪细胞的特性。它能对激素刺激做出反应,进行脂肪生成,并已成功用于研究 EDC 对脂肪生物学的影响。在这项研究中,我们对 SGBS 细胞系进行了与人类暴露相关剂量的各种 EDCs 筛选,以研究它们对细胞活力、脂质积累和脂肪生成相关蛋白表达的影响。亚微摩尔剂量的 EDCs 一般具有良好的耐受性;但剂量越大,EDCs 对细胞活力的影响越大,其中氯化镉(CdCl2)的影响最为明显。细胞内脂质水平不受 EDCs 的影响,但作为阳性对照的三丁基锡(TBT)会导致细胞内脂质水平显著增加。对脂肪生成相关蛋白质表达的分析表明了几种影响,包括邻苯二甲酸二丁酯对脂肪酸结合蛋白 4(FABP4)的下调、氯化镉对其的上调以及全氟辛酸对周脂蛋白 1 和 FABP4 的下调。此外,三丁基锡化合物可诱导 C/EBPα、周脂素 1 和 FABP4 蛋白表达的剂量依赖性上调。这些发现强调了采用适当模型研究 EDC 与脂肪细胞相互作用的重要性。这项研究的结论可以为减少暴露于 EDC 对脂肪组织的负面影响的策略提供指导。
Endocrine disruption of adipose physiology: Screening in SGBS cells
The increasing use of industrial chemicals has raised concerns regarding exposure to endocrine-disrupting chemicals (EDCs), which interfere with developmental, reproductive and metabolic processes. Of particular concern is their interaction with adipose tissue, a vital component of the endocrine system regulating metabolic and hormonal functions. The SGBS (Simpson Golabi Behmel Syndrome) cell line, a well-established human-relevant model for adipocyte research, closely mimics native adipocytes' properties. It responds to hormonal stimuli, undergoes adipogenesis and has been successfully used to study the impact of EDCs on adipose biology. In this study, we screened human exposure-relevant doses of various EDCs on the SGBS cell line to investigate their effects on viability, lipid accumulation and adipogenesis-related protein expression. Submicromolar doses were generally well tolerated; however, at higher doses, EDCs compromised cell viability, with cadmium chloride (CdCl2) showing the most pronounced effects. Intracellular lipid levels remained unaffected by EDCs, except for tributyltin (TBT), used as a positive control, which induced a significant increase. Analysis of adipogenesis-related protein expression revealed several effects, including downregulation of fatty acid-binding protein 4 (FABP4) by dibutyl phthalate, upregulation by CdCl2 and downregulation of perilipin 1 and FABP4 by perfluorooctanoic acid. Additionally, TBT induced dose-dependent upregulation of C/EBPα, perilipin 1 and FABP4 protein expression. These findings underscore the importance of employing appropriate models to study EDC-adipocyte interactions. Conclusions from this research could guide strategies to reduce the negative impacts of EDC exposure on adipose tissue.
期刊介绍:
Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.