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 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN003118 |
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Analysis type | MS |
Chromatography type | Reversed phase |
Chromatography system | Agilent 6545 LC/QTOF |
Column | Waters ACQUITY UPLC BEH C18 |
MS Type | ESI |
MS instrument type | GC-TOF |
MS instrument name | Agilent 6545 LC/QTOF |
Ion Mode | UNSPECIFIED |
Units | Summarised value |
Chromatography:
Chromatography ID: | CH002303 |
Chromatography Summary: | The extracts were analyzed on a Waters Q-Tof Premier mass spectrometer combined with an Acquity Ultra Performance LCTM. The column (at 50 °C) was an Acquity UPLCTM BEH C18 2.1 × 100 mm with 1.7 µm particles. The solvent system included A. ultrapure water (1% 1 M NH4Ac, 0.1% HCOOH) and B. LC/MS grade acetonitrile/isopropanol (1:1, 1% 1M NH4Ac, 0.1% HCOOH). The gradient started from 65% A / 35% B, reached 80% B in 2 min, 100% B in 7 min and remained there for 7 min. The flow rate was 0.400 ml/min and the injected amount was 2.0 µL (Acquity Sample Organizer, at 10 °C). Reserpine was used as the lock spray reference compound. The lipid profiling was carried out using electrospray ionization mode and the data were collected at a mass range of m/z 300-1200 with a scan duration of 0.2 sec. |
Instrument Name: | Agilent 6545 LC/QTOF |
Column Name: | Waters ACQUITY UPLC BEH C18 |
Column Temperature: | 50 |
Flow Gradient: | The gradient started from 65% A / 35% B, reached 80% B in 2 min, 100% B in 7 min and remained there for 7 min. |
Flow Rate: | 0.400 ml/min |
Solvent A: | 100% water; 0.1% formic acid; 10 mM ammonium acetate |
Solvent B: | 50% acetonitrile/50% isopropanol 0.1% formic acid; 10 mM ammonium acetate |
Chromatography Type: | Reversed phase |