ScholarWorks@중앙대학교

초록

Disruption of estrogen receptor alpha (ERα) by endocrine-active pesticides may contribute to lipid metabolic dysregulation. We aimed to clarify the docking dynamics of methiocarb with ERα and evaluate its potential to induce lipid accumulation through ERα activation using non-animal testing systems. Molecular docking predicted favorable binding between methiocarb and ERα, primarily through interactions involving the amino group. This prediction was validated using ERα reporter gene assays. Methiocarb-induced lipid accumulation was assessed in 3T3-L1 adipocytes, with or without co-treatment using the ERα antagonist methyl-piperidino-pyrazole (MPP). Methiocarb significantly activated ERα transcriptional activity and promoted ERα-dependent lipid accumulation. Co-treatment with MPP attenuated this effect, whereas antagonists for the glucocorticoid receptor (RU-486) and ERβ (PHTPP) had no effect. Methiocarb increased the expression of adipogenic and lipogenic transcription factors, including PPARγ, C/EBPα, FAS, and SREBP1, as well as the adipocyte-specific marker FABP4, in an ERα-dependent manner. Methiocarb binding to ERα promotes lipid accumulation and upregulates adipogenic/lipogenic transcriptional networks. This approach highlights the utility of ERα-mediated screening to identify potential metabolic disruptors among structurally related pesticides.

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