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Perfluorobutanesulfonic acid (PFBS) induces fat accumulation in HepG2 human hepatoma

Abstract Per- and poly-fluoroalkyl substances, especially perfluorooctanesulfonic acid (PFOS), have been extensively used for over 50 years. A growing body of evidence has emerged demonstrating the potential adverse effects of these substances, including its effect on the development of non-alcoholic fatty liver disease, as one of the most prevalent chronic liver diseases. Nonetheless, there is no report of effects of perfluorobutanesulfonic acid (PFBS), the major replacement for PFOS, on non-alcoholic fatty liver disease. Therefore, the effects of PFBS exposure on fat accumulation in a human hepatoma cell line were examined. Cells were exposed to PFBS with or without 300 μmol/L fatty acid mixture (oleic acid–palmitic acid, 2:1) conjugated by bovine serum albumin as an inducer of steatosis for 48 h. PFBS at 200 μmol/L significantly increased the triglyceride level in the presence of fatty acid compared to the control, but not without fatty acid, which was abolished by a specific peroxisome proliferator-activated receptor gamma antagonist. PFBS upregulated key genes controlling lipogenesis and fatty acid uptake. PFBS treatment also promoted the production of reactive oxygen species, an endoplasmic reticulum stress marker and cytosolic calcium. In conclusion, PFBS increased fat accumulation, in part, via peroxisome proliferator-activated receptor gamma-mediated pathway in hepatoma cells. Abbreviations: ACC: acetyl-CoA carboxylase; CD36: cluster of differentiation 36; CHOP: CCAAT/enhancer-binding homologous protein; CPT1α: carnitine palmitoyltransferase 1α; DDIT3: DNA damage-inducible transcript 3; DGAT2: diacylglycerol O-acyltransferase 2; ER: endoplasmic reticulum; FA: fatty acid; FAS: fatty acid synthase; NAFLD: nonalcoholic fatty liver disease; NF-κB: nuclear factor kappa B; PFAS: per- and polyfluoroalkyl substances; PFBS: perfluorobutanesulfonic acid; PFOS: perfluorooctanesulfonic acid; PPAR: peroxisome proliferator-activated receptor; ROS: reactive oxygen species; SREBP1: sterol regulatory element-binding protein 1; TG: triglyceride; TNF-α: tumor necrosis factor alpha; UPR: unfolded protein response