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

Author

Listed:
  • Lisa Mayr

    (Medical University of Innsbruck)

  • Felix Grabherr

    (Medical University of Innsbruck)

  • Julian Schwärzler

    (Medical University of Innsbruck)

  • Isabelle Reitmeier

    (Medical University of Innsbruck)

  • Felix Sommer

    (Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein)

  • Thomas Gehmacher

    (Medical University of Innsbruck)

  • Lukas Niederreiter

    (Medical University of Innsbruck)

  • Gui-Wei He

    (University Medical Center Erlangen)

  • Barbara Ruder

    (University Medical Center Erlangen)

  • Kai T. R. Kunz

    (Medical University of Innsbruck)

  • Piotr Tymoszuk

    (Medical University of Innsbruck)

  • Richard Hilbe

    (Medical University of Innsbruck
    Medical University of Innsbruck)

  • David Haschka

    (Medical University of Innsbruck)

  • Clemens Feistritzer

    (Medical University of Innsbruck)

  • Romana R. Gerner

    (Medical University of Innsbruck)

  • Barbara Enrich

    (Medical University of Innsbruck)

  • Nicole Przysiecki

    (Medical University of Innsbruck
    Medical University of Innsbruck)

  • Markus Seifert

    (Medical University of Innsbruck
    Medical University of Innsbruck)

  • Markus A. Keller

    (Medical University of Innsbruck)

  • Georg Oberhuber

    (Pathology Department of Innsbruck Medical University Hospital)

  • Susanne Sprung

    (Medical University of Innsbruck)

  • Qitao Ran

    (UT Health San Antonio)

  • Robert Koch

    (Medical University of Innsbruck)

  • Maria Effenberger

    (Medical University of Innsbruck)

  • Ivan Tancevski

    (Medical University of Innsbruck)

  • Heinz Zoller

    (Medical University of Innsbruck)

  • Alexander R. Moschen

    (Medical University of Innsbruck
    Medical University of Innsbruck)

  • Günter Weiss

    (Medical University of Innsbruck
    Medical University of Innsbruck)

  • Christoph Becker

    (University Medical Center Erlangen)

  • Philip Rosenstiel

    (Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein)

  • Arthur Kaser

    (University of Cambridge)

  • Herbert Tilg

    (Medical University of Innsbruck)

  • Timon E. Adolph

    (Medical University of Innsbruck)

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.

Suggested Citation

  • Lisa Mayr & Felix Grabherr & Julian Schwärzler & Isabelle Reitmeier & Felix Sommer & Thomas Gehmacher & Lukas Niederreiter & Gui-Wei He & Barbara Ruder & Kai T. R. Kunz & Piotr Tymoszuk & Richard Hilb, 2020. "Dietary lipids fuel GPX4-restricted enteritis resembling Crohn’s disease," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15646-6
    DOI: 10.1038/s41467-020-15646-6
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    Cited by:

    1. Bin Huang & Hui Wang & Shuo Liu & Meng Hao & Dan Luo & Yi Zhou & Ying Huang & Yong Nian & Lei Zhang & Bo Chu & Chengqian Yin, 2025. "Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis," Nature Communications, Nature, vol. 16(1), pages 1-19, December.

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