TY - JOUR

T1 - Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet

AU - Filipe Rosa, Louisa

AU - Rings, Andreas

AU - Stolzer, Iris

AU - Koeninger, Louis

AU - Wehkamp, Jan

AU - Beisner, Julia

AU - Günther, Claudia

AU - Nordkild, Peter

AU - Jensen, Benjamin A.H.

AU - Bischoff, Stephan C.

N1 - Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - antimicrobial peptides

KW - glucose metabolism

KW - gut barrier

KW - hBD2

KW - HD5 fragments

KW - host defense peptides

KW - NAFLD

KW - obesity

UR - http://www.scopus.com/inward/record.url?scp=85172927367&partnerID=8YFLogxK

U2 - 10.3390/ijms241813878

DO - 10.3390/ijms241813878

M3 - Journal article

C2 - 37762180

AN - SCOPUS:85172927367

VL - 24

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 18

M1 - 13878

ER -