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  Regulation of the cytochrome P450 epoxyeicosanoid pathway is associated with distinct histologic features in pediatric non-alcoholic fatty liver disease

Kalveram, L., Schunck, W.-H., Rothe, M., Rudolph, B., Loddenkemper, C., Holzhütter, H.-G., et al. (2020). Regulation of the cytochrome P450 epoxyeicosanoid pathway is associated with distinct histologic features in pediatric non-alcoholic fatty liver disease. Prostaglandins, Leukotrienes and Essential Fatty Acids, 164: 102229. doi:10.1016/j.plefa.2020.102229.

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 Creators:
Kalveram, Laura , Author
Schunck, Wolf-Hagen , Author
Rothe, Michael , Author
Rudolph, Birgit , Author
Loddenkemper, Christoph , Author
Holzhütter, Hermann-Georg , Author
Henning, Stephan , Author
Bufler, Philip , Author
Schulz, Marten , Author
Meierhofer, David1, Author              
Zhang, Ingrid W. , Author
Weylandt, Karsten H. , Author
Wiegand, Susanna , Author
Hudert, Christian A. , Author
Affiliations:
1Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

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Free keywords: Nafld Eicosanoids Cytochrome p450 Enzyme regulation Lipidomics Proteomics
 Abstract: Non-alcoholic fatty liver disease (NAFLD) is a significant health burden in obese children for which there is currently no specific therapy. Preclinical studies indicate that epoxyeicosanoids, a class of bioactive lipid mediators that are generated by cytochrome P450 (CYP) epoxygenases and inactivated by the soluble epoxide hydrolase (sEH), play a protective role in NAFLD. We performed a comprehensive lipidomics analysis using liver tissue and blood samples of 40 children with NAFLD. Proteomics was performed to determine CYP epoxygenase and sEH expressions. Hepatic epoxyeicosanoids significantly increased with higher grades of steatosis, while their precursor PUFAs were unaltered. Concomitantly, total CYP epoxygenase activity increased while protein level and activity of sEH decreased. In contrast, hepatic epoxyeicosanoids showed a strong decreasing trend with higher stages of fibrosis, accompanied by a decrease of CYP epoxygenase activity and protein expression. These findings suggest that the CYP epoxygenase/sEH pathway represents a potential pharmacologic target for the treatment of NAFLD.

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Language(s): eng - English
 Dates: 2020-12-17
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.plefa.2020.102229
 Degree: -

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Title: Prostaglandins, Leukotrienes and Essential Fatty Acids
  Abbreviation : PLEFA
Source Genre: Journal
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Affiliations:
Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 164 Sequence Number: 102229 Start / End Page: - Identifier: ISSN: 0952-3278