Effects of multiple novel bisphenol S analogs on adipogenesis in 3T3-L1 cells

The increasing usage of bisphenol S (BPS) analogs as novel alternatives to bisphenol A (BPA) or BPS results in widespread exposure risks. In contrast to BPS, BPS analog-induced perturbations in lipid metabolism are largely unknown. Our study aimed to investigate the interactions of nine novel BPS analogs with peroxisome proliferator-activated receptor γ (PPARγ) and their impacts on 3T3-L1 adipogenesis. BPS and its analogs were found to have varying binding affinities to the PPARγ ligand-binding domain, and five of the BPS analogs were identified as novel PPARγ agonists as evidenced by increased expressions of the PPARγ mediated luciferase reporter gene. Interestingly, seven BPS analogs, including five BPS analogs with PPARγ agonistic potency and two BPS analogs with negligible binding affinity, exhibited comparable or even greater adipogenic effects than BPS, which were demonstrated by increased triglyceride accumulation and enhanced expressions of the adipogenic biomarkers in 3T3-L1 cells. Further comparison revealed that a phenoxy group may be a potential structural regulator for the adipogenic capacities of the test BPS analogs. The findings provided the first evidence that seven novel BPS analogs exerted adipogenic potentials through PPARγ or other signaling pathways, revealing a hidden environmental factor in the development of obesity and other lipid metabolism disorders.