The Chemical Structure-Related Adipogenic Effects of Tetrabromobisphenol A and Its Analogs on 3T3-L1 Preadipocytes.

Tetrabromobisphenol A (TBBPA), the most widely used brominated flame retardant (BFR), is reported to potentially possess risks in inducing obesity or obesity-related metabolic diseases. Considering the increasing environmental contamination of TBBPA analogs and their high structure similarities to the parent compound, whether they could influence adipogenesis or not remains to be elucidated. In this study, two of the most prevalent TBBPA derivatives (i.e. TBBPA bis(allyl ether) (TBBPA-BAE) and TBBPA bis(2,3-dibromopropyl ether) (TBBPA-BDBPE)) and their by-products (i.e. TBBPA mono(allyl ether) (TBBPA-MAE) and TBBPA mono(2,3-dibromopropyl ether) (TBBPA-MDBPE)), together with TBBPA, were screened for their capacities in activating peroxisome proliferator-activated receptor-γ (PPARγ) and glucocorticoid receptor (GR), the key nuclear receptors involved in adipogenesis, and their structure-related effects on differentiation of 3T3-L1 preadipocytes were explored. The results indicated that the binding affinities of TBBPA and its analogs for PPARγ ligand binding domain (PPARγ-LBD) and GR, as well as their effects on PPARγ transactivation, followed the order of TBBPA > TBBPA-MAE > TBBPA-MDBPE > TBBPA-BAE, TBBPA-BDBPE. Nevertheless, TBBPA-MAE and TBBPA-MDBPE showed higher potentials in promoting adipogenesis in 3T3-L1 cells than did TBBPA, as evidenced by intracellular triglyceride contents and adipogenic biomarkers at both protein and transcriptional levels. The etherified group at position 4 of TBBPA phenolic rings was crucial in chemical-induced adipogenic effects, which was related with the recruitment of PPARγ and GR-mediated networks, and some other unidentified signaling pathways. The findings on the disturbance of TBBPA analogs on adipogenesis revealed their potential risk in causing obesity and other lipid metabolism-related human health concerns.