Bisphenol F promoted the differentiation of preadipocytes via ER-mediated PI3K/AKT pathway

Bisphenols are a group of industrial chemicals widely used in the manufacture of plastics and epoxy resins. Bisphenol F (BPF) is increasingly being used as a substitute for bisphenol A (BPA), which is a widely used environmental endocrine-disrupting chemical (EDC) and hypothesized obesogen. Nevertheless, limited research has examined the potential of BPF to induce obesity, leaving a knowledge gap. To address this issue, this study investigated the effect of BPF on the differentiation of 3T3-L1 preadipocyte and its underlying mechanisms. 3T3-L1 preadipocytes were cultured and induced to differentiate in controlled conditions, then exposed to varying BPF doses over an 8-day period. Significant increases in intracellular lipid droplets and triglyceride (TG) content were observed in the treated cells, indicating that BPF has a stimulating effect on adipogenesis. In BPF-treated 3T3-L1 preadipocytes, key adipogenic genes and proteins, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), adiponectin and fatty acid-binding protein 4 (FABP4) in 3T3-L1 preadipocytes was significantly upregulated. Further treatment with estrogen receptor (ER) antagonist ICI 182780 and PI3K inhibitor LY 294002 revealed that BPF could promote differentiation of 3T3-L1 preadipocytes through the ER mediated phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. In summary, BPF may enhance the maturation of 3T3-L1 preadipocytes by activating the ER-PI3K/AKT pathway, potentially contributing to obesity. These findings enhance the understanding of the obesogenic properties of environmental chemicals and could inform new strategies for preventing and managing obesity.