Hypercholesterolemia with Consumption of PFOA-Laced Western Diets Is Dependent on Strain and Sex of Mice
Open accessAbstract
Perfluorooctanoic acid (PFOA) is a man-made surfactant with a number of industrial applications. It has a long half-life environmentally and biologically. Past studies suggest a direct relationship between plasma cholesterol and PFOA serum concentrations in humans and an inverse one in rodents fed standard rodent chow, making it difficult to examine mechanisms responsible for the potential PFOA-induced hypercholesterolemia and altered sterol metabolism. To examine dietary modification of PFOA-induced effects, C57BL/6 and BALB/c mice were fed PFOA in a fat- and cholesterol-containing diet. When fed these high fat diets, PFOA ingestion resulted in marked hypercholesterolemia in male and female C57BL/6 mice and less robust hypercholesterolemia in male BALB/c mice. The PFOA-induced hypercholesterolemia appeared to be the result of increased liver masses and altered expression of genes associated with hepatic sterol output, specifically bile acid production. mRNA levels of genes associated with sterol input were reduced only in C57BL/6 females, the mice with the greatest increase in plasma cholesterol levels. Strain-specific PFOA-induced changes in cholesterol concentrations in mammary tissues and ovaries paralleled changes in plasma cholesterol levels. mRNA levels of sterol-related genes were reduced in ovaries of C57BL/6 but not in BALB/c mice and not in mammary tissues. Our data suggest that PFOA ingestion leads to hypercholesterolemia in mice fed fat and cholesterol and effects are dependent upon the genetic background and gender of the mice with C57BL/6 female mice being most responsive to PFOA.
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Animal studies have identified disruptions in hepatic lipid metabolism and induction of apoptosis in the liver with PFAS exposure.
“animal studies have identified disruptions in hepatic lipid metabolism and induction of apoptosis in the liver with PFAS exposure”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Rebholz et al., 2016
The Discussion reports that PFOA exposure altered expression of genes involved in liver sterol balance in mice, supporting the hepatic lipid-metabolism part of the claim. Our copy does not report induction of liver apoptosis (searched: apoptosis, apoptotic hepatocytes, liver cell death). (LLM, conf=0.87)
Experimental — accuracy not yet measuredAnimal studies have demonstrated PFAS-associated disruption of hepatic lipid metabolism, which may be mediated in part through interactions with PPARs and contribute to increased risk of NAFLD associated with PFAS exposure.
“animal studies have demonstrated PFAS associated disruption of hepatic lipid metabolism, which may be mediated, in part, through interactions with PPARs and contribute to increased risk of NAFLD associated with PFAS exposure”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Rebholz et al., 2016
The Results (page unavailable) show that PFOA altered expression of genes involved in hepatic sterol metabolism in mice fed fat- and cholesterol-containing diets. The Discussion (page unavailable) also suggests a possible role for PPARα in BALB/c mice. The paper does not connect these findings to an increased risk of NAFLD, so that part of the attributed claim is unsupported. (LLM, conf=0.87)
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References 73 · Cited by 69
Research works printed but not linked: 2
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- Authors
- Rebholz, S. L., Jones, T., Herrick, R. L., Xie, C., Calafat, A. M., Pinney, S. M., & Woollett, L. A.
- Affiliations
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Woollett, Laura A.
- Venue
- Toxicology Reports
- Publisher
- Elsevier BV
- Published
- 2016
- Volume
- 3
- Pages
- 46-54
- ISSN
- 2214-7500 (ISSN-L)
- PMC
- PMC4770828
- OpenAlex
- W2179380430
- Cited by
- 69
- References
- 73
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 5 · 2019: 9 · 2018: 4 · 2017: 3 · 2016: 1 · 2013: 1
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Toxicology Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Center for Environmental Genetics
- NIEHS
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- perfluorooctanoic acid, hypercholesterolemia, serum cholesterol, sterol metabolism, bile acid synthesis, strain differences, sex differences, C57BL/6 mice, BALB/c mice, high-fat high-cholesterol diet, mammary gland, ovary, genetic susceptibility
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