Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet

Filipe Rosa L, Rings A, Stolzer I, Koeninger L, Wehkamp J, Beisner J, Günther C, Nordkild P, Jensen BA, Bischoff SC (2023)

Publication Type: Journal article

Publication year: 2023

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 24

Article Number: 13878

Journal Issue: 18

DOI: 10.3390/ijms241813878

Abstract

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 HD51–9, 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 HD51–9 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.

Authors with CRIS profile

Iris Stolzer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Involved external institutions

Universität Hohenheim DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Defensin Therapeutics ApS DK Denmark (DK) University of Copenhagen DK Denmark (DK)

How to cite

APA:

Filipe Rosa, L., Rings, A., Stolzer, I., Koeninger, L., Wehkamp, J., Beisner, J.,... Bischoff, S.C. (2023). Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet. International Journal of Molecular Sciences, 24(18). https://dx.doi.org/10.3390/ijms241813878

MLA:

Filipe Rosa, Louisa, et al. "Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet." International Journal of Molecular Sciences 24.18 (2023).

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