ArticleArchives of toxicology2020
Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorononanoic acid (PFNA) increase triglyceride levels and decrease cholesterogenic gene expression in human HepaRG liver cells.
Article in Archives of toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 123 citations in OpenAlex.
- PFOS exposure is linked to immune-metabolic disruption in MASLD: integrated population, computational, and experimental evidence.Molecular diversity · 2026Article
- Analysis of transcriptomic alterations induced by 33 different per- and polyfluoroalkyl substances (PFAS) in differentiated HepaRG cells.Archives of toxicology · 2026Article
- Article
- Chronic PFOA and PFOS exposure triggers cellular oxidative stress and alters lipid levels as revealed through multi-omics analysis.Environmental science. Advances · 2026Article
- Identification of functional genetic components modulating toxicity response to PFOS using genome-wide CRISPR screens in HepG2/C3A cells.Archives of toxicology · 2026Article
- Forever Chemicals, Finite Defenses: PFAS Burden the Liver, Break Mitochondria, and Outpace Modern Regulation.International journal of molecular sciences · 2026Review
- Article
- Perfluorooctane sulfonic acid (PFOS) perturbs skeletal muscle oxidative phosphorylation by a different mechanism than liver.Chemosphere · 2026Article
- Impact of PFAS exposure on lipid metabolic pathways: mechanisms and implicatins in carcinogenesis.Frontiers in toxicology · 2026Review
- PFOA/PFOS induce ferroptosis in bladder epithelial cells through inhibition of ACSL4 ubiquitination.Frontiers in toxicology · 2026Article
- Identification of Functional Genetic Components Modulating Toxicity Response to PFOS using Genome-wide CRISPR Screens in HepG2/C3A cells.bioRxiv : the preprint server for biology · 2025Article
- Identification of four mechanisms of toxicity for per- and polyfluoroalkyl substances through transcriptomic profiling in human liver spheroids exposed to 24 PFAS.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Association of 6:2 Fluorotelomer Ethoxylate Exposure with Serum Lipids in General Adults.Toxics · 2025Article
- Counteracting effects of Ethanolic extract ofToxicology research · 2025Article
- Exposure to per- and poly-fluoroalkyl substances in association to later occurrence of type 2 diabetes and metabolic pathway dysregulation in a multiethnic US population.EBioMedicine · 2025Article
- 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
- Review
- Deciphering per- and polyfluoroalkyl substances mode of action: comparative gene expression analysis in human liver spheroids.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Perfluorooctanoic acid increases serum cholesterol in a PPARα-dependent manner in female mice.Archives of toxicology · 2025Article
- Placental PFAS concentrations are associated with perturbations of placental DNA methylation.Environmental pollution (Barking, Essex : 1987) · 2025Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Per- and polyfluoroalkyl substances (PFASs) are omnipresent in the environment, food chain, and humans. Epidemiological studies have shown a positive association between serum levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), and increased serum cholesterol and, in some cases, also triglyceride levels. However, causality has been questioned, as animal studies, as well as a human trial, showed a decrease in serum cholesterol and no effects or a decrease in plasma triglycerides. To obtain more insight into the effects of PFASs on these processes, the present study investigated the effects of PFOA, PFOS, and perfluorononanoic acid (PFNA) on intracellular triglyceride and cholesterol levels in human HepaRG liver cells. DNA microarray analyses were performed to provide insight into underlying mechanisms. All PFASs induced an increase in cellular triglyceride levels, but had no effect on cholesterol levels. Gene set enrichment analysis (GSEA) of the microarray data indicated that gene sets related to cholesterol biosynthesis were repressed by PFOA, PFOS, and PFNA. Other gene sets commonly affected by all PFAS were related to PERK/ATF4 signaling (induced), tRNA amino-acylation (induced), amino acid transport (induced), and glycolysis/gluconeogenesis (repressed). Moreover, numerous target genes of peroxisome proliferator-activated receptor α (PPARα) were found to be upregulated. Altogether, the present study shows that PFOA, PFOS, and PFNA increase triglyceride levels and inhibit cholesterogenic gene expression in HepaRG cells. In addition, the present study indicates that PFASs induce endoplasmic reticulum stress, which may be an important mechanism underlying some of the toxic effects of these chemicals.
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