ArticleEnvironmental toxicology2023
Per- and polyfluoroalkyl substances activate UPR pathway, induce steatosis and fibrosis in liver cells.
Article in Environmental toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Environmental PFOA Exposure Alters Early Developmental Programming during the Maternal-Zygotic Transition.bioRxiv : the preprint server for biology · 2026Article
- Presence of Legacy and Emerging PFAS in Human Liver Specimens Banked in the United States from 2000 to 2024.Environmental science & technology · 2026Article
- Recovery from chronic PFAS exposure can reverse chemotherapy resistance and mitochondrial alterations in ovarian cancer cells.Toxicology letters · 2026Article
- Early exposure to PFAS disrupts neuro-muscular development in zebrafish embryos.bioRxiv : the preprint server for biology · 2026Article
- Perfluorooctanoic acid (PFOA) induces lipid accumulation, oxidative stress, and reduced neurogenesis in primary human neuronal progenitor cells.Frontiers in toxicology · 2026Article
- Impact of PFAS exposure on lipid metabolic pathways: mechanisms and implicatins in carcinogenesis.Frontiers in toxicology · 2026Review
- Hepatic mitochondrial signaling as a systemic hub: inter-organ communication networks in aging and aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- A systems-level integration of liver-kidney transcriptomics and genome-scale metabolic models reveals organ-specific injury mechanisms.Frontiers in toxicology · 2026Article
- The maternal-to-zygotic transition is a critical window for PFOA-induced disruption of developmental programming.Frontiers in cell and developmental biology · 2026Article
- Synergistic toxicity in alcohol-associated liver disease and PFAS exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Assessing the impact of perfluoroalkyl substances on liver health: a comprehensive study using multi-donor human liver spheroids.Environment international · 2025Article
- Systemic chronic inflammation mediates the effect of per- and polyfluoroalkyl substances exposure on the risk of nonalcoholic fatty liver disease: A cross-sectional study among Chinese government employees.Environmental epidemiology (Philadelphia, Pa.) · 2025Article
- Article
- Serum lipids mediate the association of per- and polyfluoroalkyl substances exposure and age-related macular degeneration.PloS one · 2025Article
- Tributyl phosphate as a type of environmental endocrine disruptor associated with liver fibrosis: insights from NHANES andFrontiers in toxicology · 2025Article
- Unveiling the Research Void: Exploring the Reproductive Effects of PFAS Compounds on Male Health.Advances in experimental medicine and biology · 2025Review
- Effects of PFAS on human liver transporters: implications for health outcomes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Review
- The pivotal role of dysregulated autophagy in the progression of non-alcoholic fatty liver disease.Frontiers in endocrinology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Per- and polyfluoroalkyl substances (PFAS), which include perfluorooctanoic acid (PFOA), heptafluorobutyric acid (HFBA), and perfluorotetradecanoic acid (PFTA), are commonly occurring organic pollutants. Exposure to PFAS affects the immune system, thyroid and kidney function, lipid metabolism, and insulin signaling and is also involved in the development of fatty liver disease and cancer. The molecular mechanisms by which PFAS cause fatty liver disease are not understood in detail. In the current study, we investigated the effect of low physiologically relevant concentrations of PFOA, HFBA, and PFTA on cell survival, steatosis, and fibrogenic signaling in liver cell models. Exposure of PFOA and HFBA (10 to 1000 nM) specifically promoted cell survival in HepaRG and HepG2 cells. PFAS increased the expression of TNFα and IL6 inflammatory markers, increased endogenous reactive oxygen species (ROS) production, and activated unfolded protein response (UPR). Furthermore, PFAS enhanced cell steatosis and fibrosis in HepaRG and HepG2 cells which were accompanied by upregulation of steatosis (SCD1, ACC, SRBP1, and FASN), and fibrosis (TIMP2, p21, TGFβ) biomarkers expression, respectively. RNA-seq data suggested that chronic exposures to PFOA modulated the expression of fatty acid/lipid metabolic genes that are involved in the development of NFALD and fatty liver disease. Collectively our data suggest that acute/chronic physiologically relevant concentrations of PFAS enhance liver cell steatosis and fibrosis by the activation of the UPR pathway and by modulation of NFALD-related gene expression.
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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.