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Dietary lipids fuel GPX4-restricted enteritis resembling Crohn’s disease

Published version
Peer-reviewed

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Authors

Mayr, Lisa 
Grabherr, Felix 
Schwärzler, Julian 
Reitmeier, Isabelle 

Abstract

Abstract: The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn’s disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD.

Description

Keywords

Article, /631/250, /692/4020/1503/257, /13, /82/51, /13/106, article

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

11

Publisher

Nature Publishing Group UK