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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
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....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531064/ https://www.ncbi.nlm.nih.gov/pubmed/37762180 http://dx.doi.org/10.3390/ijms241813878 |
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author | Filipe Rosa, Louisa Rings, Andreas Stolzer, Iris Koeninger, Louis Wehkamp, Jan Beisner, Julia Günther, Claudia Nordkild, Peter Jensen, Benjamin A. H. Bischoff, Stephan C. |
author_facet | Filipe Rosa, Louisa Rings, Andreas Stolzer, Iris Koeninger, Louis Wehkamp, Jan Beisner, Julia Günther, Claudia Nordkild, Peter Jensen, Benjamin A. H. Bischoff, Stephan C. |
author_sort | Filipe Rosa, Louisa |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10531064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105310642023-09-28 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 Filipe Rosa, Louisa Rings, Andreas Stolzer, Iris Koeninger, Louis Wehkamp, Jan Beisner, Julia Günther, Claudia Nordkild, Peter Jensen, Benjamin A. H. Bischoff, Stephan C. Int J Mol Sci Article 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. MDPI 2023-09-09 /pmc/articles/PMC10531064/ /pubmed/37762180 http://dx.doi.org/10.3390/ijms241813878 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Filipe Rosa, Louisa Rings, Andreas Stolzer, Iris Koeninger, Louis Wehkamp, Jan Beisner, Julia Günther, Claudia Nordkild, Peter Jensen, Benjamin A. H. Bischoff, Stephan C. 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531064/ https://www.ncbi.nlm.nih.gov/pubmed/37762180 http://dx.doi.org/10.3390/ijms241813878 |
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