Summary of Study ST001919
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001210. The data can be accessed directly via it's Project DOI: 10.21228/M89D7G This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001919 |
| Study Title | Exposure to environmental contaminants is associated with alterations in hepatic lipid metabolism in non-alcoholic fatty liver disease |
| Study Summary | Background & aims: Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation and pathology of NAFLD. However, the underlying mechanisms linking EC exposure with NAFLD remain poorly understood and there is no data on their impact on the human liver metabolome. Herein, we hypothesized that exposure to ECs, particularly perfluorinated alkyl substances (PFAS), impacts liver metabolism, specifically bile acid metabolism. Methods: In a well-characterized human NAFLD cohort of 105 individuals, we investigated the effects of EC exposure on liver metabolism. We characterized the liver (via biopsy) and circulating metabolomes using four mass spectrometry-based analytical platforms, and measured PFAS and other ECs in serum. We subsequently compared these results with an exposure study in a PPARa-humanized mouse model. Results: PFAS exposure appears associated with perturbation of key hepatic metabolic pathways previously found altered in NAFLD, particularly as regards bile acid metabolism. Specifically, we identified stronger associations between the liver metabolome, chemical exposure and NAFLD-associated clinical variables in female subjects versus males. The murine exposure study further corroborated our findings, vis-à-vis a sex-specific association between PFAS exposure and NAFLD-associated lipid changes. Conclusions: Females may be more sensitive to the harmful impacts of PFAS. Lipid-related changes subsequent to PFAS exposure may be secondary to the interplay between PFAS and bile acid metabolism. |
| Institute | Örebro University |
| Department | Department of Medical Sciences |
| Last Name | McGlinchey |
| First Name | Aidan |
| Address | School of Medical Sciences, Örebro, Örebro, 70281, Sweden |
| aidan.mcglinchey@oru.se | |
| Phone | +46736485638 |
| Submit Date | 2021-09-07 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzdata.xml |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-11-03 |
| Release Version | 1 |
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Project:
| Project ID: | PR001210 |
| Project DOI: | doi: 10.21228/M89D7G |
| Project Title: | Exposure to environmental contaminants is associated with alterations in hepatic lipid metabolism in non-alcoholic fatty liver disease |
| Project Summary: | Background & aims: Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation and pathology of NAFLD. However, the underlying mechanisms linking EC exposure with NAFLD remain poorly understood and there is no data on their impact on the human liver metabolome. Herein, we hypothesized that exposure to ECs, particularly perfluorinated alkyl substances (PFAS), impacts liver metabolism, specifically bile acid metabolism. Methods: In a well-characterized human NAFLD cohort of 105 individuals, we investigated the effects of EC exposure on liver metabolism. We characterized the liver (via biopsy) and circulating metabolomes using four mass spectrometry-based analytical platforms, and measured PFAS and other ECs in serum. We subsequently compared these results with an exposure study in a PPARa-humanized mouse model. Results: PFAS exposure appears associated with perturbation of key hepatic metabolic pathways previously found altered in NAFLD, particularly as regards bile acid metabolism. Specifically, we identified stronger associations between the liver metabolome, chemical exposure and NAFLD-associated clinical variables in female subjects versus males. The murine exposure study further corroborated our findings, vis-à-vis a sex-specific association between PFAS exposure and NAFLD-associated lipid changes. Conclusions: Females may be more sensitive to the harmful impacts of PFAS. Lipid-related changes subsequent to PFAS exposure may be secondary to the interplay between PFAS and bile acid metabolism. |
| Institute: | Örebro University |
| Department: | Department of Medical Sciences |
| Last Name: | McGlinchey |
| First Name: | Aidan |
| Address: | School of Medical Sciences, Örebro, Örebro, 70281, Sweden |
| Email: | aidan.mcglinchey@oru.se |
| Phone: | +46736485638 |
