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

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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., Conti, David V., Breton, Carrie V., Liang, Donghai, Hauser, Elizabeth R., Jones, Dean P., Gilliland, Frank D.·2020·Environment International

DOI 10.1016/j.envint.2020.106091PMC PMC8009052

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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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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: Chen, Zhanghua
Yang, Tingyu
Walker, Douglas I.
Thomas, Duncan C.
Qiu, Chenyu
Chatzi, Leda
Alderete, Tanya L.
Kim, Jeniffer S.
Conti, David V.
Breton, Carrie V.
Liang, Donghai
Hauser, Elizabeth R.
Jones, Dean P.
Gilliland, Frank D.
Venue: Environment International
Publisher: Elsevier BV
Published: 2020-12
Volume: 145
Pages: 106091
ISSN: 0160-4120 (ISSN-L)
DOI: 10.1016/j.envint.2020.106091
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: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
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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Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults

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