Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults
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BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) exposure is ubiquitous among the US population and has been linked to adverse health outcomes including cardiometabolic diseases, immune dysregulation and endocrine disruption. However, the metabolic mechanism underlying the adverse health effect of PFASs exposure is unknown. OBJECTIVE: The aim of this project is to investigate the association between PFASs exposure and altered metabolic pathways linked to increased cardiometabolic risk in young adults. METHODS: A total of 102 young adults with 82% overweight or obese participants were enrolled from Southern California between 2014 and 2017. Cardiometabolic outcomes were assessed including oral glucose tolerance test (OGTT) measures, body fat and lipid profiles. High-resolution metabolomics was used to quantify plasma exposure levels of three PFAS congeners and intensity profiles of the untargeted metabolome. Fasting concentrations of 45 targeted metabolites involved in fatty acid and lipid metabolism were used to verify untargeted metabolomics findings. Bayesian Kernel Machine Regression (BKMR) was used to examine the associations between PFAS exposure mixture and cardiometabolic outcomes adjusting for covariates. Mummichog pathway enrichment analysis was used to explore PFAS-associated metabolic pathways. Moreover, the effect of PFAS exposure on the metabolic network, including metabolomic profiles and cardiometabolic outcomes, was investigated. RESULTS: Higher exposure to perfluorooctanoic acid (PFOA) was associated with higher 30-minute glucose levels and glucose area under the curve (AUC) during the OGTT (p < 0.001). PFAS exposure was also associated with altered lipid pathways, which contributed to the metabolic network connecting PFOA and higher glucose levels following the OGTT. Targeted metabolomics analysis indicated that higher PFOA exposure was associated with higher levels of glycerol (p = 0.006), which itself was associated with higher 30-minute glucose (p = 0.006). CONCLUSIONS: Increased lipolysis and fatty acid oxidation could contribute to the biological mechanisms linking PFAS exposure and impaired glucose metabolism among young adults. Findings of this study warrants future experimental studies and epidemiological studies with larger sample size to replicate.
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In young adults, exposure to PFASs, especially PFOA, has been associated with increased breakdown of fats and oxidation of fatty acids, potentially leading to disrupted glucose metabolism.
“In young adults, exposure to PFASs, especially PFOA, has been associated with increased breakdown of fats and oxidation of fatty acids, potentially leading to disrupted glucose metabolism [210].”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [210]
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- Authors
- Chen, Z., Yang, T., Walker, D. I., Thomas, D. C., Qiu, C., Chatzi, L., Alderete, T. L., Kim, J. S., Conti, D. V., Breton, C. V., Liang, D., Hauser, E. R., Jones, D. P., & Gilliland, F. D.
- Affiliations
- University of Southern California (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of Colorado Boulder (US)
- Emory University (US)
- Duke University (US)
- Corresponding author
- Chen, Zhanghua
- ORCID
- Venue
- Environment International
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 145
- Pages
- 106091
- ISSN
- 0160-4120 (ISSN-L)
- PMC
- PMC8009052
- OpenAlex
- W3083268731
- Cited by
- 176
- References
- 47
- Citations by year
- 2026: 25 · 2025: 39 · 2024: 33 · 2023: 33 · 2022: 27 · 2021: 18 · 2020: 1
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Environment International (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Environmental Health Sciences
- U.S. Environmental Protection Agency
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- per- and polyfluoroalkyl substances, PFAS exposure, perfluorooctanoic acid, impaired glucose metabolism, lipid metabolism, fatty acid metabolism, glycerol, lipolysis, fatty acid oxidation, cardiometabolic risk, young adults, obesity, oral glucose tolerance test, plasma metabolome
- MeSH terms
- Bayes Theorem, Environmental Pollutants, Fatty Acids, Fluorocarbons, Glucose, Humans, Lipids, Alkanesulfonic Acids, Lipid Metabolism, Young Adult
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