ArticleEnvironment international2021
Exposure to a mixture of legacy, alternative, and replacement per- and polyfluoroalkyl substances (PFAS) results in sex-dependent modulation of cholesterol metabolism and liver injury.
Article in Environment international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
108 citing papers in PubMed, 4 syntheses or guidelines pooled it, 272 citations in OpenAlex.
- Association between exposure to per- and polyfluoroalkyl substances and levels of lipid profile based on human studies.Reviews on environmental health · 2025Pooled it
- A metabolomic investigation of serum perfluorooctane sulfonate and perfluorooctanoate.Environment international · 2023Pooled it
- The relationship between persistent organic pollutants and Attention Deficit Hyperactivity Disorder phenotypes: Evidence from task-based neural activity in an observational study of a community sample of Canadian mother-child dyads.Environmental research · 2022Pooled it
- Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis.Environmental health perspectives · 2022Pooled it
- Association between PFAS and renal function indicators in cord blood of newborns: modifying effects of newborn sex and maternal factors.Annals of medicine · 2026Article
- Subchronic GenX Exposure Induces Hepatic Alterations Accompanied by Changes in PPAR-Related Lipid Metabolism and Autophagy-Related Proteins in Adult Male C57BL/6J Mice: Partial Attenuation by Chlorogenic Acid.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Article
- Probabilistic Concentration-Response Modeling and Risk Prioritization of Defined Mixtures of PFAS Using HumanEnvironmental science & technology · 2026Article
- Enhanced Environmental PFAS Characterization Using a Virtual High-Resolution Mass Spectral Library Generated by Transfer Learning-Based Neural Network.Environmental science & technology · 2026Article
- Review
- Placental CYP450 gene dysregulation by maternal PFAS: a novel mechanism linking prenatal exposure to altered toddler growth.Environmental health : a global access science source · 2026Article
- Single versus mixed perfluorinated compound exposures and cardiovascular disease risk: mechanistic insights from cross-sectional data and molecular interactions.Archives of toxicology · 2026Article
- Comparative study on changes in serum amino acid metabolic profiles in mice exposed to perfluorooctanoic acid and sodium ρ-perfluorous nonenoxybenzene sulfonate.Scientific reports · 2026Article
- Forever Chemicals, Finite Defenses: PFAS Burden the Liver, Break Mitochondria, and Outpace Modern Regulation.International journal of molecular sciences · 2026Review
- Increasing PFAS concentrations in human serum correlate with elevated blood lipid levels.Environmental science. Advances · 2026Article
- Per- and polyfluoroalkyl substances serum concentrations during pregnancy and gestational weight gain in the Healthy Start Study.International journal of hygiene and environmental health · 2026Article
- PFOS and PFOA exposure induces liver injury and sex-dependent immune effects in C57BL/6 mice.iScience · 2026Article
- Exposure to a PFAS mixture alters cholesterol lipoprotein subfractions and induces a foam cell-like aortic macrophage expression profile in hyperlipidemic LDLrToxicology and applied pharmacology · 2026Article
- Mechanistic Insights and Design Strategies for Hydrogel/Aerogel Sorbents in Remediation of Per- and Polyfluoroalkyl Substances.ACS environmental Au · 2026Review
- Sorption of Anionic and Zwitterionic Per- and Polyfluoroalkyl Substances Present in Legacy Aqueous Film-Forming Foams.Environmental science & technology · 2026Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEpidemiological studies have shown Per- and polyfluoroalkyl substances (PFAS) to be associated with diseases of dysregulated lipid and sterol homeostasis such as steatosis and cardiometabolic disorders. However, the majority of mechanistic studies rely on single chemical exposures instead of identifying mechanisms related to the toxicity of PFAS mixtures.
objectivesThe goal of the current study is to investigate mechanisms linking exposure to a PFAS mixture with alterations in lipid metabolism, including increased circulating cholesterol and bile acids.
methodsMale and female wild-type C57BL/6J mice were fed an atherogenic diet used in previous studies of pollutant-accelerated atherosclerosis and exposed to water containing a mixture of 5 PFAS representing legacy, replacement, and alternative subtypes (i.e., PFOA, PFOS, PFNA, PFHxS, and GenX), each at a concentration of 2 mg/L, for 12 weeks. Changes at the transcriptome and metabolome level were determined by RNA-seq and high-resolution mass spectrometry, respectively.
resultsWe observed increased circulating cholesterol, sterol metabolites, and bile acids due to PFAS exposure, with some sexual dimorphic effects. PFAS exposure increased hepatic injury, demonstrated by increased liver weight, hepatic inflammation, and plasma alanine aminotransferase levels. Females displayed increased lobular and portal inflammation compared to the male PFAS-exposed mice. Hepatic transcriptomics analysis revealed PFAS exposure modulated multiple metabolic pathways, including those related to sterols, bile acids, and acyl carnitines, with multiple sex-specific differences observed. Finally, we show that hepatic and circulating levels of PFOA were increased in exposed females compared to males, but this sexual dimorphism was not the same for other PFAS examined. DISCUSSION: Exposure of mice to a mixture of PFAS results in PFAS-mediated modulation of cholesterol levels, possibly through disruption of enterohepatic circulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.