Transcriptomic analysis of HepG2 cells treated with BDE-47, BDE-99, BDE-209 and their ternary mixture at 1nM as a dietary relevant concentration

ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals implied as flame re-tardants. Humans are mainly exposed to BDE-47, -99 and -209 congeners by diet. PBDEs are metabolic disruptors with liver as main target organ. To investigate their mode of action at a human relevant concentration, we exposed HepG2 cells to these congeners and their mixture at 1 nM for 72h, analyzing their transcriptomic and proteomic profiles. KEGG pathways and GSEA Hallmarks enrichment analyses evidenced that BDE-47 disrupted the glucose metabolism and Hypoxia pathway; all the congeners and the MIX affected lipid metabolism and signaling Hallmarks regulating metabolism as mTORC1 and PI3K/AKT/MTOR. These results were confirmed by glucose secretion depletion and increased lipid accumulation, especially in BDE-47 and -209 treated cells. These congeners also affected the EGFR/MAPK signaling; further, BDE-47 enriched the Estrogen pathway. Interestingly, BDE-209 and the MIX increased ERα gene expression, whereas all the congeners and the MIX induced ERβ and PPARγ. We also found that PBDEs modulated several lncRNAs and that HNRNAP1 represented a central hub in all the four interaction networks. Overall, despite the low concentration used, the PBDEs investigated affected glucose and lipid metabolism with different underlying modes of action, as highlighted by the integrated omics analysis. These results may support the mechanism-based risk assessment of these compounds in relation to liver metabolism disruption.

ORGANISM(S): Homo sapiens

PROVIDER: GSE216590 | GEO | 2022/10/28

REPOSITORIES: GEO