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

Abstract

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 ERα-HeLa-9903 cell line, through binding affinity to ERα. 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 (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and perilipin expression. Furthermore, PPARγ, C/EBPα 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.

Keywords: Adipogenesis; Agonist; Estrogen receptor; Organophosphorus pesticides.