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

Autor: Richard Hilbe, Lukas Niederreiter, Ivan Tancevski, Qitao Ran, Piotr Tymoszuk, Barbara Enrich, Maria Effenberger, Lisa Mayr, Barbara Ruder, Thomas Gehmacher, Kai T.R. Kunz, Philip Rosenstiel, Clemens Feistritzer, Christoph Becker, Alexander R. Moschen, Felix Grabherr, Susanne Sprung, David Haschka, N Przysiecki, Robert Koch, Herbert Tilg, Markus Seifert, Gui-Wei He, Julian Schwärzler, Isabelle Reitmeier, Felix Sommer, Arthur Kaser, Markus A. Keller, Romana R. Gerner, Günter Weiss, Heinz Zoller, Georg Oberhuber, Timon E. Adolph
Přispěvatelé: Sommer, Felix [0000-0002-6545-3487], Tymoszuk, Piotr [0000-0002-0398-6034], Keller, Markus A. [0000-0002-8654-9920], Moschen, Alexander R. [0000-0003-3598-7848], Weiss, Günter [0000-0003-0709-2158], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
General Physics and Astronomy
GPX4
13
Inflammatory bowel disease
Lipid peroxidation
chemistry.chemical_compound
Mice
0302 clinical medicine
Crohn Disease
lcsh:Science
chemistry.chemical_classification
Crohn's disease
Multidisciplinary
Cell Death
631/250
Middle Aged
Intestinal epithelium
Enteritis
030220 oncology & carcinogenesis
Fatty Acids
Unsaturated
692/4020/1503/257
Arachidonic acid
Female
Polyunsaturated fatty acid
Adult
Science
Immunology
13/106
digestive system
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
medicine
Animals
Humans
Inflammation
Glutathione Peroxidase
business.industry
General Chemistry
medicine.disease
Phospholipid Hydroperoxide Glutathione Peroxidase
Dietary Fats
digestive system diseases
Mice
Inbred C57BL
030104 developmental biology
chemistry
lcsh:Q
Lipid Peroxidation
business
82/51
Zdroj: Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020)
Nature Communications
ISSN: 2041-1723
Popis: 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.
Dietary lipids are linked to the development of inflammatory bowel diseases through unclear mechanisms. Here, the authors report that dietary polyunsaturated fatty acids trigger intestinal inflammation resembling aspects of Crohn’s disease, which is restricted by glutathione peroxidase 4 in the intestinal epithelium.
Databáze: OpenAIRE
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