دورية أكاديمية
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Microbial metabolite deoxycholic acid-mediated ferroptosis exacerbates high-fat diet-induced colonic inflammation.

التفاصيل البيبلوغرافية
العنوان: Microbial metabolite deoxycholic acid-mediated ferroptosis exacerbates high-fat diet-induced colonic inflammation.
المؤلفون: Wang C; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China., Chu Q; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China., Dong W; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China., Wang X; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China., Zhao W; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China., Dai X; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China., Liu W; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China., Wang B; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China., Liu T; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China. Electronic address: liutianyu@tmu.edu.cn., Zhong W; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China. Electronic address: zhongweilong@tmu.edu.cn., Jiang C; Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing, China. Electronic address: jiangchangtao@bjmu.edu.cn., Cao H; Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China. Electronic address: caohailong@tmu.edu.cn.
المصدر: Molecular metabolism [Mol Metab] 2024 Jun; Vol. 84, pp. 101944. Date of Electronic Publication: 2024 Apr 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier GmbH Country of Publication: Germany NLM ID: 101605730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2212-8778 (Electronic) Linking ISSN: 22128778 NLM ISO Abbreviation: Mol Metab Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [München] : Elsevier GmbH, 2012-
مواضيع طبية MeSH: Deoxycholic Acid*/metabolism , Deoxycholic Acid*/pharmacology , Deoxycholic Acid*/adverse effects , Diet, High-Fat*/adverse effects , Ferroptosis*/drug effects , Mice, Inbred C57BL*, Animals ; Mice ; Male ; Humans ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Inflammation/metabolism ; Colitis/metabolism ; Colitis/chemically induced ; Colitis/pathology ; Colon/metabolism ; Colon/pathology ; Colitis, Ulcerative/metabolism ; Colitis, Ulcerative/chemically induced ; Colitis, Ulcerative/pathology ; Gastrointestinal Microbiome/drug effects ; Mice, Knockout
مستخلص: High-fat diet (HFD) has long been recognized as risk factors for the development and progression of ulcerative colitis (UC), but the exact mechanism remained elusive. Here, HFD increased intestinal deoxycholic acid (DCA) levels, and DCA further exacerbated colonic inflammation. Transcriptome analysis revealed that DCA triggered ferroptosis pathway in colitis mice. Mechanistically, DCA upregulated hypoxia-inducible factor-2α (HIF-2α) and divalent metal transporter-1 (DMT1) expression, causing the ferrous ions accumulation and ferroptosis in intestinal epithelial cells, which was reversed by ferroptosis inhibitor ferrostatin-1. DCA failed to promote colitis and ferroptosis in intestine-specific HIF-2α-null mice. Notably, byak-angelicin inhibited DCA-induced pro-inflammatory and pro-ferroptotic effects through blocking the up-regulation of HIF-2α by DCA. Moreover, fat intake was positively correlated with disease activity in UC patients consuming HFD, with ferroptosis being more pronounced. Collectively, our findings demonstrated that HFD exacerbated colonic inflammation by promoting DCA-mediated ferroptosis, providing new insights into diet-related bile acid dysregulation in UC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
فهرسة مساهمة: Keywords: Byak-angelicin; Colitis; Deoxycholic acid; Ferroptosis; HIF-2α/DMT1; High-fat diet
المشرفين على المادة: 005990WHZZ (Deoxycholic Acid)
0 (Basic Helix-Loop-Helix Transcription Factors)
1B37H0967P (endothelial PAS domain-containing protein 1)
تواريخ الأحداث: Date Created: 20240420 Date Completed: 20240522 Latest Revision: 20240522
رمز التحديث: 20240523
مُعرف محوري في PubMed: PMC11070703
DOI: 10.1016/j.molmet.2024.101944
PMID: 38642891
قاعدة البيانات: MEDLINE
الوصف
تدمد:2212-8778
DOI:10.1016/j.molmet.2024.101944