ArticleToxicology and applied pharmacology2016
The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction.
Article in Toxicology and applied pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- The effect of PFAS exposure on glucolipid metabolism in children and adolescents: a meta-analysis.Frontiers in endocrinology · 2024Pooled it
- SINEUP-mediated enhancement of HNF4α improves metabolic function in Huh7-based bioengineered hepatic microtissues.Journal of liver cancer · 2026Article
- Article
- Associations of Serum Per- and Polyfluoroalkyl Substance Concentrations with Dyslipidemia and Its Subtypes in an Adult Population from Shandong, East China.Environment & health (Washington, D.C.) · 2026Article
- New Mechanistic Evidence for Perfluorodecanoic Acid (PFDA) Teratogenicity via CYP26A1-Mediated Retinoic Acid Metabolism and Signaling.Chemical research in toxicology · 2026Article
- Perfluorooctane Sulfonate (PFOS) Disrupts Mitochondrial Activity and Cell Adhesion in Liver Cells.Journal of xenobiotics · 2026Article
- Impact of PFAS exposure on lipid metabolic pathways: mechanisms and implicatins in carcinogenesis.Frontiers in toxicology · 2026Review
- Models and challenges for studying forever chemicals and their impact on human health.Disease models & mechanisms · 2025Review
- Association of 6:2 Fluorotelomer Ethoxylate Exposure with Serum Lipids in General Adults.Toxics · 2025Article
- Toxicokinetics and Perfluorooctanesulfonic Acid-Induced Liver Protein Expression Are Markedly Altered in Mice Lacking Albumin.Chemical research in toxicology · 2025Article
- Comparison of phenotypic and transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in wild-type and Ppara-null mouse livers.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
- In vitro screening of understudied PFAS with a focus on lipid metabolism disruption.Archives of toxicology · 2024Article
- Identifying novel mechanisms of per- and polyfluoroalkyl substance-induced hepatotoxicity using FRG humanized mice.Archives of toxicology · 2024Article
- Effects of PFAS on human liver transporters: implications for health outcomes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Exposure ofEnvironmental health perspectives · 2024Article
- Occurrence of COVID-19 and serumGlobal epidemiology · 2024Article
- Involvement of per- and polyfluoroalkyl compounds in tumor development.Archives of toxicology · 2024Review
- Exposure to PFAS chemicals induces sex-dependent alterations in key rate-limiting steps of lipid metabolism in liver steatosis.Frontiers in toxicology · 2024Article
- The Association of Perfluoroalkyl Substance Exposure and a Serum Liver Function Marker in Korean Adults.Toxics · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), chemicals present in a multitude of consumer products, are persistent organic pollutants. Both compounds induce hepatotoxic effects in rodents, including steatosis, hepatomegaly and liver cancer. The mechanisms of PFOA- and PFOS-induced hepatic dysfunction are not completely understood. We present evidence that PFOA and PFOS induce their hepatic effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α). Human hepatocytes treated with PFOA and PFOS at a concentration relevant to occupational exposure caused a decrease in HNF4α protein without affecting HNF4α mRNA or causing cell death. RNA sequencing analysis combined with Ingenuity Pathway Analysis of global gene expression changes in human hepatocytes treated with PFOA or PFOS indicated alterations in the expression of genes involved in lipid metabolism and tumorigenesis, several of which are regulated by HNF4α. Further investigation of specific HNF4α target gene expression revealed that PFOA and PFOS could promote cellular dedifferentiation and increase cell proliferation by down regulating positive targets (differentiation genes such as CYP7A1) and inducing negative targets of HNF4α (pro-mitogenic genes such as CCND1). Furthermore, in silico docking simulations indicated that PFOA and PFOS could directly interact with HNF4α in a similar manner to endogenous fatty acids. Collectively, these results highlight HNF4α degradation as novel mechanism of PFOA and PFOS-mediated steatosis and tumorigenesis in human livers.
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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.