Potential obesogenic effects of TBBPA and its alternatives TBBPS and TCBPA revealed by metabolic perturbations in human hepatoma cells

• Published in: The Science of the total environment Vol. 832; p. 154847
• Main Authors: Yu, Yunjiang, Hao, Chaojie, Xiang, Mingdeng, Tian, Jinglin, Kuang, Hongxuan, Li, Zhenchi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2022
• Subjects: Brominated flame retardants; Metabolomics; Obesogens; Sugar metabolism; Tetrabromobisphenol A; Metabolomics; Obesogens; Sugar metabolism; Tetrabromobisphenol A; Brominated flame retardants
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2022.154847

To date, increasing numbers of studies have shown the obesogenic effects of tetrabromobisphenol A (TBBPA). Tetrabromobisphenol S (TBBPS) and tetrachlorobisphenol A (TCBPA) are two common alternatives to TBBPA, and their environmental distributions are frequently reported. However, their toxicity and the associated potential health risks are poorly documented. Herein, we performed untargeted metabolomics to study the metabolic perturbations in HepG2 cells exposed to TBBPA and its alternatives. Consequently, no loss of cellular viability was observed in HepG2 cells exposed to 0.1 μmol/L and 1 μmol/L TBBPA, TBBPS and TCBPA. However, multivariate analysis and metabolic profiles revealed significant perturbations in glycerophospholipid and fatty acyl levels in HepG2 cells exposure to TBBPS and TCBPA. The evident increases in the glucose 1-phosphate and fructose 6-phosphate levels in HepG2 cells were proposed to be induced by the promotion of PGM1/PGM2 and GPI gene expression and the suppression of UPG2 and GFPT1/GFPT2 gene expression. Our results suggest that TBBPS and TCBPA are more likely to disrupt liver metabolic homeostasis and potentially drive liver dysfunction than TBBPA. Our study is significant for the re-evaluation of the health risks associated with TBBPA and its alternatives TBBPS and TCBPA.
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•TBBPA, TBBPS, and TCBPA induced significant metabolic changes in HepG2 cells.•Glycerophospholipid and fatty acyl were perturbated by the TBBPS at 0.1 μmol/L.•TBBPS and TCBPA induced PGM1/PGM2 promotion and GFPT1/GFPT2 suppression in cells.•Sugar metabolisms in HepG2 cells were more sensitive to TBBPS and TCBPA than TBBPA.