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

Environment International

Tingyu Yang¹  Duncan C. Thomas²  Jeniffer S. Kim³  Frank D. Gilliland⁴  David V. Conti⁵  Chenyu Qiu⁶  Carrie V. Breton⁶  Tanya L. Alderete⁷  Donghai Liang⁷  Douglas I. Walker⁷  Zhanghua Chen⁷  Leda Chatzi⁷  Dean P. Jones⁸  Elizabeth R. Hauser⁹ 

[1] Corresponding author at: Southern California Environmental Health Sciences Center, Department of Preventive Medicine, University of Southern California, Keck School of Medicine of USC, 2001 N. Soto Street 230F, Los Angeles, CA 90032, USA.;Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO, USA;Department of Medicine, Emory University, Atlanta, GA, USA;Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA;Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA;Division of Environmental Health, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA;Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center Durham, NC, USA;Rollins School of Public Health, Emory University, Atlanta, GA, USA;

关键词: Perfluoroalkyl substances;    Cardiometabolic dysfunction;    Metabolomics;    β-oxidation;    Lipolysis;    Young adults;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown