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 |
|---|---|
| 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 |
MS:
| MS ID: | MS002899 |
| Analysis ID: | AN003118 |
| Instrument Name: | Agilent 6545 LC/QTOF |
| Instrument Type: | GC-TOF |
| MS Type: | ESI |
| MS Comments: | The data processing included alignment of peaks, peak integration, normalization and identification. Lipids were identified using an internal spectral library. The data were normalized using one or more internal standards representative of each class of lipid present in the samples: the intensity of each identified lipid was normalized by dividing it with the intensity of its corresponding standard and multiplying it by the concentration of the standard. All monoacyl lipids except cholesterol esters, such as monoacylglycerols and monoacylglycerophospholipids, were normalized with PC(17:0/0:0), all diacyl lipids except ethanolamine phospholipids were normalized with PC(17:0/17:0), all ceramides with Cer(d18:1/17:0), all diacyl ethanolamine phospholipids with PE(17:0/17:0), and TG and cholesterol esters with TG(17:0/17:0/17:0). Other (unidentified) molecular species were normalized with PC(17:0/0:0) for retention times < 300 s, PC(17:0/17:0) for a retention time between 300 s and 410 s, and TG(17:0/17:0/17:0) for longer retention times. Quality control of the method showed that the day-to-day repeatability of control serum samples, and the relative standard deviation (RSD) for values identified was on average below 25% and 20% for discovery and validation sECs, respectively. The internal standards added to all samples in the study had an average RSD of 25% and 13 % in the discovery and validation sECs. |
| Ion Mode: | UNSPECIFIED |
