Plasma concentrations of per- and polyfluoroalkyl substances are associated with perturbations in lipid and amino acid metabolism

Prince, Nicole; Begum, Sofina; Mínguez-Alarcón, Lidia; Génard-Walton, Maximilien; Huang, Mengna; Soeteman, Djøra I.; Wheelock, Craig E.; Litonjua, Augusto A.; Weiss, Scott T.; Kelly, Rachel S.; Lasky‐Su, Jessica

doi:10.1016/j.chemosphere.2023.138228

Cited by 10 publications

(10 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Metabolomics is the systemic study of all metabolites associated with exogenous exposure and endogenous processes, and has emerged as an innovative and powerful analytical platform in environmental epidemiology. , Recent investigations demonstrate the applicability of using metabolomics as a central platform to link human exposure with internal dose and biological response. − Specifically, an increase in circulating concentrations of PFAS has been consistently associated with several endocrine disruption- and oxidative stress-related pathways. ,,− In one of our recent metabolome-wide association studies (MWAS), we also identified and verified several biomechanisms and biomarkers mediating the association between serum PFAS concentrations and fetal growth restriction . Moreover, in two separate analyses within the same pregnant population, we found an inverse association between prenatal exposure to PFAS, modeled as single chemicals and a mixture, with fetal growth measures. , …”

Section: Introductionmentioning

confidence: 73%

Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort

Liang,

Taibl,

Dunlop

et al. 2023

Environ. Sci. Technol.

View full text Add to dashboard Cite

Prenatal exposure to single chemicals belonging to the per-and polyfluoroalkyl substances (PFAS) family is associated with biological perturbations in the mother, fetus, and placenta, plus adverse health outcomes. Despite our knowledge that humans are exposed to multiple PFAS, the potential joint effects of PFAS on the metabolome remain largely unknown. Here, we leveraged high-resolution metabolomics to identify metabolites and metabolic pathways perturbed by exposure to a PFAS mixture during pregnancy. Targeted assessment of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS), along with untargeted metabolomics profiling, were conducted on nonfasting serum samples collected from pregnant African Americans at 6−17 weeks gestation. We estimated the overall mixture effect and partial effects using quantile g-computation and single-chemical effects using linear regression. All models were adjusted for maternal age, education, parity, early pregnancy body mass index, substance use, and gestational weeks at sample collection. Our analytic sample included 268 participants and was socioeconomically diverse, with the majority receiving public health insurance (78%). We observed 13.3% of the detected metabolic features were associated with the PFAS mixture (n = 1705, p < 0.05), which was more than any of the single PFAS chemicals. There was a consistent association with metabolic pathways indicative of systemic inflammation and oxidative stress (e.g., glutathione, histidine, leukotriene, linoleic acid, prostaglandins, and vitamins A, C, D, and E metabolism) across all metabolome-wide association studies. Twenty-six metabolites were validated against authenticated compounds and associated with the PFAS mixture (p < 0.05). Based on quantile g-computation weights, PFNA contributed the most to the overall mixture effect for γ-aminobutyric acid (GABA), tyrosine, and uracil. In one of the first studies of its kind, we demonstrate the feasibility and utility of using methods designed for exposure mixtures in conjunction with metabolomics to assess the potential joint effects of multiple PFAS chemicals on the human metabolome. We identified more pronounced metabolic perturbations associated with the PFAS mixture than for single PFAS chemicals. Taken together, our findings illustrate the potential for integrating environmental mixture analyses and high-throughput metabolomics to elucidate the molecular mechanisms underlying human health.

show abstract

Section: Introductionmentioning

confidence: 73%

Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort

Liang,

Taibl,

Dunlop

et al. 2023

Environ. Sci. Technol.

View full text Add to dashboard Cite

show abstract

“…They observed significant associations for mostly amino acid pathways; these pathways included arginine, proline, and lysine metabolism but not glutamine metabolism or valine, leucine, and isoleucine degradation. Additionally, a cross-sectional study evaluating 459 pregnant people in the VDAART Study also found that lipid and amino acid pathways were significantly associated with a mixture of PFOA, PFOS, PFDEA, PFHxS, and PFNA and the maternal metabolome, measured in late trimester blood plasma . Another cross-sectional study evaluating four PFAS individually (PFHxS, PFOS, PFOA, or PFNA) and the maternal metabolome (serum between 8- to 14-weeks’ gestation) in 313 African-American people found a considerable number of enriched pathways overlapping the pathways identified in our study (amino acid metabolism, glycan biosynthesis and metabolism, carbohydrate metabolism, lipid metabolism, and metabolism of cofactors and vitamins) .…”

Section: Resultsmentioning

confidence: 99%

“…Results from our study are largely consistent with previous studies examining prenatal PFAS or PFAS mixtures in relation to the maternal or infant metabolome, with the most consistent associations observed for the amino acid and lipid metabolism. 22,24,58,59 Taibl et al evaluated associations of late pregnancy PFOA, PFNA, PFOS, or PFHxS concentrations with the infant metabolome (measured via blood spots within 48 h of birth) for 267 mother−child pairs in African-American women in Atlanta Georgia between 2016 and 2020. 59 They observed significant associations for mostly amino acid pathways; these pathways included arginine, proline, and lysine metabolism but not glutamine metabolism or valine, leucine, and isoleucine degradation.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…While numerous statistical methods have been developed to quantify the potential effects of chemical mixtures, few studies have evaluated the impact of PFAS mixtures on the fetal metabolome. − Understanding the impact of PFAS exposures on the fetal metabolome is important because PFAS can cross the placenta, and the fetus may be more sensitive to environmental exposures compared to later life stages . Furthermore, the investigation of chemical mixtures is critical, given that PFAS exposure does not occur in isolation.…”

Section: Introductionmentioning

confidence: 99%

“…Untargeted metabolomics is a discovery-based technique that comprehensively assesses metabolic profiles and pathways . In tandem with statistical tools like metabolome-wide association studies (MWAS) and pathway enrichment analysis, relations between exposures to PFAS and hundreds to thousands of metabolites and their corresponding biological pathways can be investigated. − As such, untargeted metabolomics is being increasingly used to identify metabolites and pathways associated with human exposure or disease …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Associations of a Prenatal Serum Per- and Polyfluoroalkyl Substance Mixture with the Cord Serum Metabolome in the HOME Study

Hall,

Fleury,

Papandonatos

et al. 2023

Environ. Sci. Technol.

View full text Add to dashboard Cite

An Integrated Metabolomics‐Based Model, and Identification of Potential Biomarkers, of Perfluorooctane Sulfonic Acid Toxicity in Zebrafish Embryos

Annunziato,

Bashirova,

Eeza

et al. 2024

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

Known for their high stability and surfactant properties, per‐ and polyfluoroalkyl substances (PFAS) have been widely used in a range of manufactured products. Despite being largely phased out due to concerns regarding their persistence, bioaccumulation, and toxicity, legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid continue to persist at high levels in the environment, posing risks to aquatic organisms. We used high‐resolution magic angle spinning nuclear magnetic resonance spectroscopy in intact zebrafish (Danio rerio) embryos to investigate the metabolic pathways altered by PFOS both before and after hatching (i.e., 24 and 72 h post fertilization [hpf], respectively). Assessment of embryotoxicity found embryo lethality in the parts‐per‐million range with no significant difference in mortality between the 24‐ and 72‐hpf exposure groups. Metabolic profiling revealed mostly consistent changes between the two exposure groups, with altered metabolites generally associated with oxidative stress, lipid metabolism, energy production, and mitochondrial function, as well as specific targeting of the liver and central nervous system as key systems. These metabolic changes were further supported by analyses of tissue‐specific production of reactive oxygen species, as well as nontargeted mass spectrometric lipid profiling. Our findings suggest that PFOS‐induced metabolic changes in zebrafish embryos may be mediated through previously described interactions with regulatory and transcription factors leading to disruption of mitochondrial function and energy metabolism. The present study proposes a systems‐level model of PFOS toxicity in early life stages of zebrafish, and also identifies potential biomarkers of effect and exposure for improved environmental biomonitoring. Environ Toxicol Chem 2024;00:1–19. © 2024 SETAC

show abstract

Plasma concentrations of per- and polyfluoroalkyl substances are associated with perturbations in lipid and amino acid metabolism

Cited by 10 publications

References 44 publications

Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort

Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort

Associations of a Prenatal Serum Per- and Polyfluoroalkyl Substance Mixture with the Cord Serum Metabolome in the HOME Study

An Integrated Metabolomics‐Based Model, and Identification of Potential Biomarkers, of Perfluorooctane Sulfonic Acid Toxicity in Zebrafish Embryos

Contact Info

Product

Resources

About