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.

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Study IDST001919
Study TitleExposure to environmental contaminants is associated with alterations in hepatic lipid metabolism in non-alcoholic fatty liver disease
Study SummaryBackground & 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
DepartmentDepartment of Medical Sciences
Last NameMcGlinchey
First NameAidan
AddressSchool of Medical Sciences, Örebro, Örebro, 70281, Sweden
Emailaidan.mcglinchey@oru.se
Phone+46736485638
Submit Date2021-09-07
Raw Data AvailableYes
Raw Data File Type(s)mzdata.xml
Analysis Type DetailLC-MS
Release Date2021-11-03
Release Version1
Aidan McGlinchey Aidan McGlinchey
https://dx.doi.org/10.21228/M89D7G
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Cohort Mouse Sex Genotype Ear Mark Treatment
SA1778300060_LC_20190903_sample_00312 10 Female KO 1x Rt PFOA
SA1778310060_LC_20190903_sample_00382 11 Male KO 1x Lt Vh
SA1778320060_LC_20190903_sample_00302 12 Male hPPARa None Vh
SA1778330060_LC_20190903_sample_00092 13 Male hPPARa 1x Rt PFOA
SA1778340060_LC_20190903_sample_00122 8 Female KO 1x Lt Vh
SA1778350060_LC_20190903_sample_00212 9 Female hPPARa None PFOA
SA1778360060_LC_20190903_sample_00113 14 Male KO None Vh
SA1778370060_LC_20190903_sample_00293 15 Male hPPARa 1x Rt Vh
SA1778380060_LC_20190903_sample_00023 16 Female hPPARa None Vh
SA1778390060_LC_20190903_sample_00083 17 Female KO 1x Rt Vh
SA1778400060_LC_20190903_sample_00163 18 Female hPPARa 1x Lt Vh
SA1778410060_LC_20190903_sample_00063 19 Female hPPARa 1x Bt Vh
SA1778420060_LC_20190903_sample_00254 20 Male hPPARa 1x Rt PFOA
SA1778430060_LC_20190903_sample_00224 21 Male KO 2x Rt PFOA
SA1778440060_LC_20190903_sample_00334 22 Female KO 1x Lt PFOA
SA1778450060_LC_20190903_sample_00365 23 Female KO None PFOA
SA1778460060_LC_20190903_sample_00345 24 Female KO 1x Rt PFOA
SA1778470060_LC_20190903_sample_00175 25 Female hPPARa 1x Lt PFOA
SA1778480060_LC_20190903_sample_00325 26 Female hPPARa 1x Bt PFOA
SA1778490060_LC_20190903_sample_00275 27 Male KO None PFOA
SA1778500060_LC_20190903_sample_00285 28 Male hPPARa 1x Rt PFOA
SA1778510060_LC_20190903_sample_00265 29 Male KO 1x Lt PFOA
SA1778520060_LC_20190903_sample_00416 30 Male hPPARa 1x Rt Vh
SA1778530060_LC_20190903_sample_00356 31 Male hPPARa 1x Lt Vh
SA1778540060_LC_20190903_sample_00186 32 Male KO 1x Bt Vh
SA1778550060_LC_20190903_sample_00076 33 Female KO None Vh
SA1778560060_LC_20190903_sample_00106 34 Female KO 1x Rt Vh
SA1778570060_LC_20190903_sample_00046 35 Female KO 1x Lt Vh
SA1778580060_LC_20190903_sample_00406 36 Female hPPARa 1x Bt Vh
SA1778590060_LC_20190903_sample_00236 37 Male hPPARa None PFOA
SA1778600060_LC_20190903_sample_00147 38 Male hPPARa None Vh
SA1778610060_LC_20190903_sample_00157 39 Male hPPARa 1x Rt Vh
SA1778620060_LC_20190903_sample_00397 40 Male hPPARa 1x Lt Vh
SA1778630060_LC_20190903_sample_00037 41 Male KO 1x Bt Vh
SA1778640060_LC_20190903_sample_00137 42 Female hPPARa None PFOA
SA1778650060_LC_20190903_sample_00058 43 Male hPPARa None PFOA
SA1778660060_LC_20190903_sample_00018 44 Female hPPARa 1x Lt PFOA
SA1778670060_LC_20190903_sample_00208 45 Female KO 1x Bt PFOA
SA1778680060_LC_20190903_sample_00378 46 Female hPPARa 2x Rt PFOA
SA1778690060_LC_20190903_sample_00248 47 Female hPPARa None Vh
SA1778700060_LC_20190903_sample_00198 48 Female hPPARa 1x Rt Vh
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