ArticleToxicology and applied pharmacology2022
Replacement per- and polyfluoroalkyl substances (PFAS) are potent modulators of lipogenic and drug metabolizing gene expression signatures in primary human hepatocytes.
Article in Toxicology and applied pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 50 citations in OpenAlex.
- Forever Chemicals, Finite Defenses: PFAS Burden the Liver, Break Mitochondria, and Outpace Modern Regulation.International journal of molecular sciences · 2026Review
- Perfluorooctane sulfonic acid (PFOS) perturbs skeletal muscle oxidative phosphorylation by a different mechanism than liver.Chemosphere · 2026Article
- Synergistic toxicity in alcohol-associated liver disease and PFAS exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Molecular Determinants of Per- and Polyfluoroalkyl Substances Binding to Estrogen Receptors.Toxics · 2025Article
- Review
- Legacy, alternative, and precursor PFAS and associations with lipids and liver function biomarkers: results from a cross-sectional analysis of adult females in the MIREC-ENDO study.International journal of hygiene and environmental health · 2025Article
- Risk of serum circulating environmental chemical residues to esophageal squamous cell carcinoma: a nested case-control metabolome-wide association study.Analytical and bioanalytical chemistry · 2025Article
- Serum PFAS and lipid concentrations in Ecuadorian adolescents.Archives of environmental & occupational health · 2025Article
- Associations of perfluoroalkyl substances with metabolic-associated fatty liver disease and non-alcoholic fatty liver disease: NHANES 2017-2018.Cancer causes & control : CCC · 2024Article
- Effects of PFAS on human liver transporters: implications for health outcomes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Hazard and risk characterization of 56 structurally diverse PFAS using a targeted battery of broad coverage assays using six human cell types.Toxicology · 2024Article
- Impact of perfluoroalkyl substances (PFAS) and PFAS mixtures on lipid metabolism in differentiated HepaRG cells as a model for human hepatocytes.Archives of toxicology · 2024Article
- Article
- Systemic toxicity induced by topical application of perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), and perfluoropentanoic acid (PFPeA) in a murine model.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Article
- Assessment of Mouse Liver Histopathology Following Exposure to HFPO-DA With Emphasis on Understanding Mechanisms of Hepatocellular Death.Toxicologic pathology · 2023Article
- Exposure to low-dose perfluorooctanoic acid promotes hepatic steatosis and disrupts the hepatic transcriptome in mice.Molecular metabolism · 2022Article
- Metabolomic, Lipidomic, Transcriptomic, and Metagenomic Analyses in Mice Exposed to PFOS and Fed Soluble and Insoluble Dietary Fibers.Environmental health perspectives · 2022Article
- Review
- Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefighters.Epigenomics · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Per- and polyfluoroalkyl substances (PFAS) are a class of environmental toxicants, and some, such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), have been associated with hepatic steatosis in rodents and monkeys. It was hypothesized that perfluorosulfonic acids (C4, 6, 8), perfluorocarboxylic acids (C4-14), perfluoro(2-methyl-3-oxahexanoic) acid (HFPO-DA), 1H, 1H, 2H, 2H-perfluorooctanesulfonic acid (6:2 FTS) along with 3 PFOS precursors could induce expression of lipid metabolism genes and lipid deposition in human hepatocytes. Five-donor pooled cryopreserved human hepatocytes were cultured and treated with 0.1% DMSO vehicle or various PFAS (0.25 to 25 μM) in media. After a 48-h treatment, mRNA transcripts related to lipid transport, metabolism, and synthesis were measured using a Quantigene Plex assay. After 72-h treatments, hepatocytes were stained with Nile Red dye to quantify intracellular lipids. Overall, PFAS were transcriptionally active at 25 μM. In this model, lipid accumulation was not observed with C8-C12 treatments. Shorter chain PFAS (C4-C5), 6:2 FTS, and PFOS precursor, metFOSA, induced significant liver lipid accumulation, and gene activation at lower concentrations than legacy PFAS. In summary short chain PFAS and other alternative PFAS were more potent gene inducers, and potential health effects of replacement PFAS should be critically evaluated in humans.
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Registered trials
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