Bisphenol S induces lipid metabolic disruption associated with SREBP signaling in Caenorhabditis elegans.

Bisphenol S (BPS) is a widely used substitute for bisphenol A (BPA). In recent years, the detection frequency of BPS in various environmental media and biological matrices has been increasing, raising widespread concern regarding its potential adverse effects on metabolic health. However, the molecular mechanisms underlying BPS-induced metabolic toxicity remain incompletely understood. In this study, Caenorhabditis elegans (C. elegans) was employed as an in vivo model to systematically evaluate the bioaccumulation characteristics and metabolic toxicity of BPS, with bioinformatics analyses integrated to provide mechanistic support. The results showed that following continuous 3-day exposure, BPS accumulated significantly in C. elegans and induced a range of metabolic disturbances, including increased triglyceride (TG) and reactive oxygen species (ROS) levels, decreased ATP content, altered fatty acid composition, and dysregulated expression of lipid metabolism-related genes (fat-6, fat-7, sbp-1, mdt-15, fasn-1, and acs-2). Functional analysis using RNA interference (RNAi) further identified SBP-1, a core regulator of lipid homeostasis, as a key mediator of BPS-induced metabolic toxicity. Complementary molecular docking and molecular dynamics simulations supported the structural plausibility of interactions between BPS and SREBF1, the human homolog of SBP-1/SREBP. In addition, virtual screening analyses indicated that certain natural flavonoids may exhibit comparative binding affinity toward SREBF1. Overall, these findings suggest that BPS exposure may be associated with disruption of lipid homeostasis through the SREBF1/SREBP signaling axis and indicate potential metabolic health implications.