Evidence map›Paper›PMID 41365295›Full record

ArticleCell metabolism2026

Metabolic stress sensing by epithelial RXRα links westernization of diet with Crohn's disease.

Moritz Meyer, Felix Grabherr, Christina Plattner, Michel V Hadjihannas, Zhigang Rao, Valentin Marteau, Víctor Alonso López-Agudelo, Julian Schwärzler, Lisa Mayr, Almina Jukic and 30 more

Abstract read
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In one paragraph

Article in Cell metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors.

Moritz MeyerDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Felix GrabherrDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Christina PlattnerBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.
Michel V HadjihannasInstitute of Clinical Molecular Biology, Christian Albrechts University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany.
Zhigang RaoMichael Popp Institute and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria.
Valentin MarteauBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.
Víctor Alonso López-AgudeloInstitute of Clinical Molecular Biology, Christian Albrechts University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany.
Julian SchwärzlerDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Lisa MayrDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Almina JukicDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Laura ScheffauerDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Luis ZundelDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Barbara EnrichDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Alexandra PfisterDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Anna SimoniniDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Christoph GranderDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Richard HilbeDepartment of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.
David HaschkaDepartment of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.
Andreas ZollnerDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Kathrin VoukDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Patrizia MoserINNPATH, Innsbruck Medical University Hospital, Innsbruck, Austria.
Michael W HessInstitute of Histology and Embryology, Medical University of Innsbruck, Innsbruck, Austria.
Niloofar NematiBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.
Dietmar RiederBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.
Felix SommerInstitute of Clinical Molecular Biology, Christian Albrechts University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany.
Philip RosenstielInstitute of Clinical Molecular Biology, Christian Albrechts University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany.
Qitao RanDepartment of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX, USA.
Richard S BlumbergGastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Arthur KaserDivision of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Florian RiederDepartment of Gastroenterology, Hepatology & Nutrition, Digestive Diseases Institute, Department of Inflammation and Immunity, Lerner Research Institute, Center for Global Translational Inflammatory Bowel Disease Research, Cleveland Clinic Foundation, Cleveland, OH, USA.
Andreas KoeberleMichael Popp Institute and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria; Institute of Pharmaceutical Sciences and Excellence Field BioHealth, NAWI Graz, University of Graz, Graz, Austria.
Christoph BeckerDepartment of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Raja AtreyaDepartment of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Anja A KühlCharité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, iPATH.Berlin, Berlin, Germany.
Britta SiegmundCharité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Germany.
Andre FrankeInstitute of Clinical Molecular Biology, Christian Albrechts University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany.
IBDome Consortium
Herbert TilgDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Zlatko TrajanoskiBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.
Timon E AdolphDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: timon-erik.adolph@i-med.ac.at.

Funding

The Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI Theresa Torres Pizarro · 2015 to 2026
$15.6M
Endoplasmic reticulum stress and intestinal inflammationR01DK088199 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Richard S Blumberg · 2010 to 2026
$9.6M
NIDDK NIH HHS P30 DK097948NIDDK NIH HHS R01 DK088199
6 · The paper itself

Abstract

Westernization of diet, partly characterized by long-chain fatty acid excess, perturbs intestinal immune responses in Crohn's disease (CD). The cellular and molecular framework of lipid sensing in intestinal inflammation remains enigmatic. By small intestinal transcriptional profiling of CD, we identified increased transcriptional activity of retinoid X receptor alpha (RXRα) specifically in intestinal epithelial cells (IECs). Transcriptional RXRα activity was induced in IECs of mice by ω-3 and ω-6 polyunsaturated fatty acid (PUFA) excess in a Western diet. PUFA-induced RXRα activity in Paneth cells governed chronic transmural enteritis by enabling the expression of CXCL1. Oral exposure to isotretinoin ameliorated PUFA-induced metabolic enteritis in two mouse models, and isotretinoin therapy reduced the odds of developing CD in an analysis of electronic health care records from 170,597 patients. Collectively, we identify RXRα in Paneth cells as a metabolic stress sensor that enables enteritis, providing novel perspectives for the prevention and treatment of CD.

Indexed as

Crohn DiseaseDiet, WesternEpithelial CellsRetinoid X Receptor alphaStress, PhysiologicalAnimalsDisease Models, AnimalFatty Acids, Omega-3FemaleHumansIntestinal MucosaMaleMiceMice, Inbred C57BLPaneth CellsFatty Acids, Omega-3Retinoid X Receptor alphaCDCrohn’s diseaseIBDinflammatory bowel diseasesintestinal inflammationmetabolic inflammationPaneth cellretinoid X receptor alphaRXRaWestern diet

Identifiers

PMID41365295
PMCPMC13034575

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.