Acrylamide (ACR) is generated during thermal processing of carbohydrate-rich foods at high temperature and can directly enter the body through ingestion, inhalation and skin contact. The toxicity of ACR has been widely studied. The main results of these studies show that exposure to ACR can cause neurotoxicity in both animals and humans, and show reproductive toxicity and carcinogenicity in rodent animal models. However, the mechanism of toxicity of ACR has not been studied by metabolomics approaches, and the effect of ACR on autophagy remains unknown. Here, U₂OS cell were treated with ACR 6 and 24 h and collected for further study. We have demonstrated that ACR inhibited autophagic flux, and increased ROS content. Accumulation of ROS resulted in increase of apoptosis rates and secretion of inflammatory factors. In addition, significant differences in metabolic profiles were observed between ACR treated and control cells according to multiple analysis models. A total of 73 key differential metabolites were identified. They were involved in multiple metabolic pathways. Among them, exposure to ACR caused glycolysis/gluconeogenesis attenuation by decreasing levels of glycolytic intermediates, reduced the rate of the TCA cycle, while elevating levels of several amino acid metabolites and lipid metabolites. In summary, our study provides useful evidence of cytotoxicity caused by ACR via metabolomics and multiple bioanalytic methods.

丙烯酰胺（ACR）是在富含碳水化合物的食物于高温下进行热处理的过程中产生的，可通过摄入，吸入和皮肤接触直接进入人体。ACR的毒性已被广泛研究。这些研究的主要结果表明，暴露于ACR可以在动物和人类中引起神经毒性，并在啮齿动物模型中显示出生殖毒性和致癌性。但是，尚未通过代谢组学方法研究ACR的毒性机制，并且ACR对自噬的影响仍然未知。在这里，U ₂OS细胞用ACR 6和24小时处理并收集用于进一步研究。我们已经证明，ACR抑制自噬通量，并增加ROS含量。ROS的积累导致细胞凋亡率增加和炎症因子的分泌。此外，根据多种分析模型，在ACR处理的细胞和对照细胞之间观察到代谢谱的显着差异。总共鉴定出73种关键的差异代谢产物。他们参与了多种代谢途径。其中，暴露于ACR会通过降低糖酵解中间体的水平，降低TCA循环速率，同时提高几种氨基酸代谢物和脂质代谢物的水平而引起糖酵解/糖异生。综上所述，