Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 125 Ruijin Er Road, Shanghai, 200025, China.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, China.
Environ Sci Pollut Res Int. 2018 Jun;25(17):17050-17057. doi: 10.1007/s11356-018-1921-6. Epub 2018 Apr 9.
2,4-Dichlorophenoxyacetic acid is one of the most widely used herbicides. Its impact on health is increasingly attracting great attentions. This study aimed to investigate the effect of 2,4-dichlorophenoxyacetic acid on glucose metabolism in HepG2 cells and the underlying mechanism. After 24 h exposure to 2,4-dichlorophenoxyacetic acid, glycogen was measured by PAS staining and glucose by ELISA in HepG2 cells. The expression of genes involved in glucose metabolism was measured by real-time PCR, Western blotting, and immunofluorescence. HepG2 cells presented more extracellular glucose consumption and glycogen content after exposed to 2,4-dichlorophenoxyacetic acid. Expression of gluconeogenesis-related genes, FoxO1, and CREB is significantly elevated. Moreover, PPARβ was up-regulated dose-dependently. SiRNA knockdown of PPARβ completely rescued the increase of glycogen accumulation and glucose uptake, and the up-regulation of FOXO1 and CREB expression. Our findings propose novel mechanisms that 2,4-dichlorophenoxyacetic acid causes glucose metabolism dysfunction through PPARβ in HepG2 cells.
2,4-二氯苯氧乙酸是应用最广泛的除草剂之一。其对健康的影响越来越受到关注。本研究旨在探讨 2,4-二氯苯氧乙酸对 HepG2 细胞葡萄糖代谢的影响及其作用机制。用 2,4-二氯苯氧乙酸处理 HepG2 细胞 24 小时后，通过 PAS 染色法测定糖原，ELISA 法测定葡萄糖。实时 PCR、Western blot 和免疫荧光法测定与葡萄糖代谢相关基因的表达。用 2,4-二氯苯氧乙酸处理后，HepG2 细胞表现出更多的细胞外葡萄糖消耗和糖原含量。糖异生相关基因 FoxO1 和 CREB 的表达明显升高。此外，PPARβ 呈浓度依赖性地上调。PPARβ 的 siRNA 敲低可完全挽救糖原积累和葡萄糖摄取的增加，以及 FOXO1 和 CREB 表达的上调。我们的研究结果提出了新的机制，即 2,4-二氯苯氧乙酸通过 HepG2 细胞中的 PPARβ 导致葡萄糖代谢功能障碍。
