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Exposure to environ...
Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease
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- Sen, Partho, 1983- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Qadri, Sami (författare)
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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- Luukkonen, Panu K. (författare)
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Internal Medicine, Yale University, New Haven, Connecticut, USA
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- Ragnarsdottir, Oddny (författare)
- School of Science and Technology, Örebro University, Örebro, Sweden,MTM Research Centre
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- McGlinchey, Aidan J, 1984- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper
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- Jäntti, Sirkku (författare)
- Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
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- Juuti, Anne (författare)
- Department of Gastrointestinal Surgery, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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- Arola, Johanna (författare)
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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- Schlezinger, Jennifer J. (författare)
- Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA
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- Webster, Thomas F. (författare)
- Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA
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- Oresic, Matej, 1967- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Yki-Järvinen, Hannele (författare)
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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- Hyötyläinen, Tuulia, 1971- (författare)
- Örebro universitet,Institutionen för naturvetenskap och teknik,MTM Research Centre
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(creator_code:org_t)
- Elsevier, 2022
- 2022
- Engelska.
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 76:2, s. 283-293
- Relaterad länk:
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https://doi.org/10.1...
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http://www.journal-o...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background & aims: Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation and pathology of non-alcoholic fatty liver disease (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 4 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 those related to bile acid and lipid metabolism. We identified stronger associations between the liver metabolome, chemical exposure and NAFLD-associated clinical variables (liver fat content, HOMA-IR), in females than males. Specifically, we observed PFAS-associated upregulation of bile acids, triacylglycerols and ceramides, and association between chemical exposure and dysregulated glucose metabolism in females. 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.Lay summary: There is increasing evidence that specific environmental contaminants, such as perfluorinated alkyl substances (PFAS), contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, it is poorly understood how these chemicals impact human liver metabolism. Here we show that human exposure to PFAS impacts metabolic processes associated with NAFLD, and that the effect is different in females and males.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)
Nyckelord
- chemical exposure
- exposome
- perfluorinated alkyl substance
- non- alcoholic steatohepatitis
- fibrosis
- bile acid
- lipidome
- metabolome
- metabolic pathway
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Sen, Partho, 198 ...
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Qadri, Sami
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Luukkonen, Panu ...
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Ragnarsdottir, O ...
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McGlinchey, Aida ...
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Jäntti, Sirkku
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visa fler...
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Juuti, Anne
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Arola, Johanna
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Schlezinger, Jen ...
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Webster, Thomas ...
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Oresic, Matej, 1 ...
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Yki-Järvinen, Ha ...
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Hyötyläinen, Tuu ...
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Örebro universitet