Evaluation of PFHxS, PFOA, PFOS, and PFNA impact on liver metabolism using human liver spheroids

Accumulating evidence suggests that poly- and perfluoroalkyl substances (PFAS), a class of persistent organic pollutants, cause changes in hepatic lipid, amino acid, and glucose metabolism. Our study explores the molecular mechanisms whereby PFHxS, PFOA, PFOS, and PFNA disrupt liver metabolism. Overall design: 3D InSightTM human liver spheroids (InSphero) composed of hepatocytes (10 donors: 5 males and 5 females), endothelial cells, and macrophages (1 donor). Liver spheroids were maintained in low glucose medium (lean medium) were exposed to 20µM of PFHxS, PFOA, PFOS, or PFNA for 7 days. Control spheroids were cultured in lean medium for the same time. We dissociated spheroids with Trypsin, generating suitable cells for 10x genomics scRNAseq (kit 3' v3.1).