Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease
Mayr L, Grabherr F, Schwrzler J, Reitmeier I, Sommer F, Gehmacher T, Niederreiter L, He GW, Ruder B, Kunz KTR, Tymoszuk P, Hilbe R, Haschka D, Feistritzer C, Gerner RR, Enrich B, Przysiecki N, Seifert M, Keller MA, Oberhuber G, Sprung S, Ran Q, Koch R, Effenberger M, Tancevski I, Zoller H, Moschen AR, Weiss G, Becker C, Rosenstiel P, Kaser A, Tilg H, Adolph TE (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 11
Journal Issue: 1
DOI: 10.1038/s41467-020-15646-6
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 omega-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.
Authors with CRIS profile
Involved external institutions
Medizinische Universität Innsbruck
Austria (AT)
Christian-Albrechts-Universität zu Kiel
Germany (DE)
University of Texas Health Science Center at San Antonio (UTHSCSA)
United States (USA) (US)
Klinik der Medizinischen Universität Innsbruck
Austria (AT)
University of Cambridge
United Kingdom (GB)
Austria (AT)
Christian-Albrechts-Universität zu Kiel
Germany (DE)
University of Texas Health Science Center at San Antonio (UTHSCSA)
United States (USA) (US)
Klinik der Medizinischen Universität Innsbruck
Austria (AT)
University of Cambridge
United Kingdom (GB)
How to cite
APA:
Mayr, L., Grabherr, F., Schwrzler, J., Reitmeier, I., Sommer, F., Gehmacher, T.,... Adolph, T.E. (2020). Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-15646-6
MLA:
Mayr, Lisa, et al. "Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease." Nature Communications 11.1 (2020).
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