Cited by 176Per- and polyfluoroalkyl substances researchMetabolomics and Mass Spectrometry StudiesPeroxisome Proliferator-Activated Receptors

Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults

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Chen, Zhanghua, Yang, Tingyu, Walker, Douglas I., Thomas, Duncan C., Qiu, Chenyu, Chatzi, Leda, Alderete, Tanya L., Kim, Jeniffer S. +6 more·2020·Environment International

Abstract

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].”

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Research works printed but not linked: 2

  1. Patsouris D, Mandard S, Voshol PJ,, 2004. PPARalpha governs glycerol metabolism. J. Clin. Invest 114, 94– 103. 15232616 PMC437964
  2. Salihovic S, Fall T, Ganna A,, 2019. Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances. J. Eposure Sci. Environ. Epidemiol 29, 196– 205. 30185940

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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
Venue
Environment International
Publisher
Elsevier BV
Published
2020-12
Volume
145
Pages
106091
ISSN
0160-4120 (ISSN-L)
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
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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