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

Item Type:	Article
Title:	Regulation of the cytochrome P450 epoxyeicosanoid pathway is associated with distinct histologic features in pediatric non-alcoholic fatty liver disease
Creators Name:	Kalveram, L. and Schunck, W.H. and Rothe, M. and Rudolph, B. and Loddenkemper, C. and Holzhütter, H.G. and Henning, S. and Bufler, P. and Schulz, M. and Meierhofer, D. and Zhang, I.W. and Weylandt, K.H. and Wiegand, S. and Hudert, C.A.
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.
Keywords:	NAFLD, Eicosanoids, CYP P450, Enzyme Regulation, Lipidomics, Proteomics
Source:	Prostaglandins Leukotrienes and Essential Fatty Acids
ISSN:	0952-3278
Publisher:	Elsevier
Volume:	164
Page Range:	102229
Date:	January 2021
Official Publication:	https://doi.org/10.1016/j.plefa.2020.102229
PubMed:	View item in PubMed

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