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Human α-Defensin 5 1-9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet.

التفاصيل البيبلوغرافية
العنوان: Human α-Defensin 5 1-9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet.
المؤلفون: Filipe Rosa L; Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599 Stuttgart, Germany., Rings A; Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599 Stuttgart, Germany., Stolzer I; Department of Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), Universitätsklinikum Erlangen, 91054 Erlangen, Germany., Koeninger L; Department of Internal Medicine I, University Hospital Tübingen, 72016 Tübingen, Germany., Wehkamp J; Department of Internal Medicine I, University Hospital Tübingen, 72016 Tübingen, Germany., Beisner J; Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599 Stuttgart, Germany., Günther C; Department of Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), Universitätsklinikum Erlangen, 91054 Erlangen, Germany., Nordkild P; Defensin Therapeutics, 2200 Copenhagen, Denmark., Jensen BAH; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1353 Copenhagen, Denmark., Bischoff SC; Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599 Stuttgart, Germany.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2023 Sep 09; Vol. 24 (18). Date of Electronic Publication: 2023 Sep 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مستخلص: Obesity and metabolic comorbidities are associated with gut permeability. While high-fructose and Western-style diet (WSD) disrupt intestinal barrier function, oral administration of human α-defensin 5 (HD5) and β-defensin 2 (hBD2) is believed to improve intestinal integrity and metabolic disorders. Eighty-four male C57BL/6J mice were fed a WSD or a control diet (CD) ± fructose (F) for 18 weeks. In week 13, mice were randomly divided into three intervention groups, receiving defensin fragment HD5 1-9 , full-length hBD2, or bovine serum albumin (BSA)-control for six weeks. Subsequently, parameters of hepatic steatosis, glucose metabolism, and gut barrier function were assessed. WSDF increased body weight and hepatic steatosis ( p < 0.01) compared to CD-fed mice, whereas peptide intervention decreased liver fat ( p < 0.05) and number of hepatic lipid droplets ( p < 0.01) compared to BSA-control. In addition, both peptides attenuated glucose intolerance by reducing blood glucose curves in WSDF-fed mice. Evaluation of gut barrier function revealed that HD5 1-9 and hBD2 improve intestinal integrity by upregulating tight junction and mucin expression. Moreover, peptide treatment restored ileal host defense peptides (HDP) expression, likely by modulating the Wnt, Myd88, p38, and Jak/STAT pathways. These findings strongly suggest that α- and β-defensin treatment improve hepatic steatosis, glucose metabolism, and gut barrier function.
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فهرسة مساهمة: Keywords: HD5 fragments; NAFLD; antimicrobial peptides; glucose metabolism; gut barrier; hBD2; host defense peptides; obesity
تواريخ الأحداث: Date Created: 20230928 Latest Revision: 20231003
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10531064
DOI: 10.3390/ijms241813878
PMID: 37762180
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms241813878