Organophosphorus pesticides exert estrogen receptor agonistic effect determined using Organization for Economic Cooperation and Development PBTG455, and induce estrogen receptor-dependent adipogenesis of 3T3-L1 adipocytes

Various chemicals containing pesticides can induce adipogenesis and cause obesity. Organophosphorus pesticides have been used for pest control. Here, we investigated the estrogen receptor (ER)-dependent adipogenesis-inducing effect of representative organophosphorus pesticides (OPs), diazinon, phoxim, terbufos and tolclofos-methyl in 3T3-L1 adipocytes. Four OPs exhibited ER agonistic effect, determined using the OECD Performance Based Test Guideline No. 455; in vitro ER stably transfected transactivation assay using ER alpha-HeLa-9903 cell line, through binding affinity to ER alpha. Additionally, they increased lipid droplet accumulation in a dose-dependent manner, which was suppressed by ICI182,780, a well-known ER antagonist. Four OPs treatment induced peroxisome proliferator-activated receptor gamma (PPAR gamma), CCAAT/enhancer-binding protein alpha (C/EBP alpha), and perilipin expression. Furthermore, PPAR gamma, C/EBP alpha and perilipin expression was inhibited by co-treatment with ICI182,780. The increased mRNA expression of lipoprotein lipase and fatty acid synthase by four OPs was suppressed by co-treatment with ICI182,780. These results indicated that diazinon, phoxim, terbufos, and tolclofos-methyl might have adipogenesis-inducing effect mediated by interacting with ER. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The study revealed that four organophosphorus pesticides may induce adipogenesis by interacting with the estrogen receptor, leading to lipid droplet accumulation and regulation of gene expression related to fat metabolism.