ArticleToxicology and applied pharmacology2020
Perfluorooctanoic acid activates multiple nuclear receptor pathways and skews expression of genes regulating cholesterol homeostasis in liver of humanized PPARα mice fed an American diet.
Article in Toxicology and applied pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- The effect of PFAS exposure on glucolipid metabolism in children and adolescents: a meta-analysis.Frontiers in endocrinology · 2024Pooled it
- Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis.Environmental health perspectives · 2022Pooled it
- A Review on Environmental Occurrence and Toxicity of Perfluorooctanoic Acid and Its Selected Short-Chain Analogs-Perfluorohexanoic Acid and Perfluorobutanoic Acid.International journal of molecular sciences · 2026Review
- Developmental exposure to a PFAS mixture impairs the anamnestic response to influenza A virus infection in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Forever Chemicals, Finite Defenses: PFAS Burden the Liver, Break Mitochondria, and Outpace Modern Regulation.International journal of molecular sciences · 2026Review
- 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
- Per- and polyfluoroalkyl substances (PFAS) exposure and cardiovascular risk: lipid profile as a mediator.Lipids in health and disease · 2025Article
- Perfluoroalkyl Substances (PFAS) and Lipid Metabolism in Experimental Animal Models: A Scoping Review on the Mechanisms Behind the Induced Hepatotoxicity.Current issues in molecular biology · 2025Review
- Developmental exposure to a PFAS mixture impairs the anamnestic response to influenza A virus infection in mice.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
- Investigating Lipid and Energy Dyshomeostasis Induced by Per- and Polyfluoroalkyl Substances (PFAS) Congeners in Mouse Model Using Systems Biology Approaches.Metabolites · 2025Article
- Suppression effect of folate on poly- and perfluoroalkyl substance-induced alterations in lipids and the atherogenic index of plasma in adolescents.Lipids in health and disease · 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
- Perfluorooctanoic acid increases serum cholesterol in a PPARα-dependent manner in female mice.Archives of toxicology · 2025Article
- Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis.Chemical research in toxicology · 2025Article
- Extracellular Vesicle (EV) Mechanisms of Toxicity for Per and Polyfluoroalkyl Substances: Comparing Transcriptomic Points of Departure Across Global Versus EV Regulatory Gene Sets.Environmental and molecular mutagenesis · 2025Article
- An oat fiber intervention for reducing PFAS body burden: A pilot study in male C57Bl/6 J mice.Toxicology and applied pharmacology · 2025Article
- Per- and Polyfluoroalkyl Substances and Outcomes Related to Metabolic Syndrome: A Review of the Literature and Current Recommendations for Clinicians.American journal of lifestyle medicine · 2025Review
- Article
- Associations of per- and polyfluoroalkyl substances with human milk metabolomic profiles in a rural North American cohort.Environmental epidemiology (Philadelphia, Pa.) · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Humans are exposed to per- and polyfluoroalkyl substances (PFAS) in their drinking water, food, air, dust, and by direct use of consumer products. Increased concentrations of serum total cholesterol and low density lipoprotein cholesterol are among the endpoints best supported by epidemiology. The objectives of this study were to generate a new model for examining PFAS-induced dyslipidemia and to conduct molecular studies to better define mechanism(s) of action. We tested the hypothesis that perfluorooctanoic acid (PFOA) exposure at a human-relevant level dysregulates expression of genes controlling cholesterol homeostasis in livers of mice expressing human PPARα (hPPARα). Female and male hPPARα and PPARα null mice were fed a diet based on the "What we eat in America" analysis and exposed to PFOA in drinking water (8 μM) for 6 weeks. This resulted in a serum PFOA concentration of 48 μg/ml. PFOA increased liver mass, which was associated with histologically-evident lipid accumulation. Pooled analyses of serum lipoprotein cholesterol suggest that PFOA increased serum cholesterol, particularly in male mice. PFOA induced PPARα and constitutive androstane receptor target gene expression in liver. Expression of genes in four pathways regulating cholesterol homeostasis were also measured. PFOA decreased expression of Hmgcr in a PPARα-dependent manner. PFOA decreased expression of Ldlr and Cyp7a1 in a PPARα-independent manner. Apob expression was not changed. Sex differences were evident. This novel study design (hPPARα mice, American diet, long term exposure) generated new insight on the effects of PFOA on cholesterol regulation in the liver and the role of hPPARα.
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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 OpenQuestion graph.