@article{4197a78f7c9749c9afde8ae5358a7d02,
title = "Dietary lipids fuel GPX4-restricted enteritis resembling Crohn{\textquoteright}s disease",
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{\textquoteright}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.",
author = "Lisa Mayr and Felix Grabherr and Julian Schw{\"a}rzler and Isabelle Reitmeier and Felix Sommer and Thomas Gehmacher and Lukas Niederreiter and He, {Gui Wei} and Barbara Ruder and Kunz, {Kai T.R.} and Piotr Tymoszuk and Richard Hilbe and David Haschka and Clemens Feistritzer and Gerner, {Romana R.} and Barbara Enrich and Nicole Przysiecki and Markus Seifert and Keller, {Markus A.} and Georg Oberhuber and Susanne Sprung and Qitao Ran and Robert Koch and Maria Effenberger and Ivan Tancevski and Heinz Zoller and Moschen, {Alexander R.} and G{\"u}nter Weiss and Christoph Becker and Philip Rosenstiel and Arthur Kaser and Herbert Tilg and Adolph, {Timon E.}",
note = "Funding Information: The authors are grateful for the support received from the Austrian Science Fund (FWF, P 29379-B28), the Tyrolean Science Fund (TWF, 0404/1812), the Austrian Society of Gastroenterology and Hepatology ({\"O}GGH) and the European Crohn{\textquoteright}s and Colitis Organisation (ECCO) (to T.E.A.). We thank the Excellence Initiative (Competence Centers for Excellent Technologies—COMET) of the Austrian Research Promotion Agency FFG: Research Center of Excellence in Vascular Ageing Tyrol, VASCage (K-Project Nr. 843536) funded by BMVIT, BMWFW, Wirtschaftsagentur Wien and Standortagentur Tirol for their financial support (to H.T.). This work was further supported by the German Funding Agency (DFG) through the CRC1182 (C2 to F.S. & P.R.), the excellence initiative EXC306 (to P.R.) and EXS2167 (to P.R.). We thank the German Funding Agency (DFG) through TRR241 (A03 to C.B.) and SFB1181 (C05 to C.B.). We appreciate the support of the Christian Doppler Research Foundation and the Austrian Federal Ministry of Science, Research and Economy and the National Foundation for Research, Technology and Development (to A.R.M and G.W.). We thank Cornelia Wiedner Stiftung and Deutsche Arbeitsgemeinschaft f{\"u}r chronisch entz{\"u}ndliche Dar-merkrankungen (DACED) for financial support (to T.E.A). Finally, we thank Karina Greve and the IKMB NGS lab for excellent technical support. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-15646-6",
language = "English (US)",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}