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

Publication ,  Journal Article
Chen, Z; Yang, T; Walker, DI; Thomas, DC; Qiu, C; Chatzi, L; Alderete, TL; Kim, JS; Conti, DV; Breton, CV; Liang, D; Hauser, ER; Jones, DP ...
Published in: Environ Int
December 2020

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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Published In

Environ Int

DOI

EISSN

1873-6750

Publication Date

December 2020

Volume

145

Start / End Page

106091

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Lipids
  • Lipid Metabolism
  • Humans
  • Glucose
  • Fluorocarbons
  • Fatty Acids
  • Environmental Sciences
  • Environmental Pollutants
  • Bayes Theorem
 

Citation

APA
Chicago
ICMJE
MLA
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Chen, Z., Yang, T., Walker, D. I., Thomas, D. C., Qiu, C., Chatzi, L., … Gilliland, F. D. (2020). Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults. Environ Int, 145, 106091. https://doi.org/10.1016/j.envint.2020.106091
Chen, Zhanghua, Tingyu Yang, Douglas I. Walker, Duncan C. Thomas, Chenyu Qiu, Leda Chatzi, Tanya L. Alderete, et al. “Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults.Environ Int 145 (December 2020): 106091. https://doi.org/10.1016/j.envint.2020.106091.
Chen Z, Yang T, Walker DI, Thomas DC, Qiu C, Chatzi L, et al. Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults. Environ Int. 2020 Dec;145:106091.
Chen, Zhanghua, et al. “Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults.Environ Int, vol. 145, Dec. 2020, p. 106091. Pubmed, doi:10.1016/j.envint.2020.106091.
Chen Z, Yang T, Walker DI, Thomas DC, Qiu C, Chatzi L, Alderete TL, Kim JS, Conti DV, Breton CV, Liang D, Hauser ER, Jones DP, Gilliland FD. Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults. Environ Int. 2020 Dec;145:106091.
Journal cover image

Published In

Environ Int

DOI

EISSN

1873-6750

Publication Date

December 2020

Volume

145

Start / End Page

106091

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Lipids
  • Lipid Metabolism
  • Humans
  • Glucose
  • Fluorocarbons
  • Fatty Acids
  • Environmental Sciences
  • Environmental Pollutants
  • Bayes Theorem