Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease

Abstract Toll-like receptors (TLRs) in the liver compartment have repeatedly been attributed to the development of non-alcoholic fatty liver disease (NAFLD). Knowledge on TLR expression in blood cells and their relation to intestinal microbiota and NAFLD development is limited. Here, we determined T...

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Autores principales:	Anja Baumann, Anika Nier, Angélica Hernández-Arriaga, Annette Brandt, Maria J. Lorenzo Pisarello, Cheng J. Jin, Esther Pilar, Amélia Camarinha-Silva, Jörn M. Schattenberg, Ina Bergheim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4bf6f872572040e897d0b276027d7f17
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spelling	oai:doaj.org-article:4bf6f872572040e897d0b276027d7f172021-12-02T19:13:48ZToll-like receptor 1 as a possible target in non-alcoholic fatty liver disease10.1038/s41598-021-97346-92045-2322https://doaj.org/article/4bf6f872572040e897d0b276027d7f172021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97346-9https://doaj.org/toc/2045-2322Abstract Toll-like receptors (TLRs) in the liver compartment have repeatedly been attributed to the development of non-alcoholic fatty liver disease (NAFLD). Knowledge on TLR expression in blood cells and their relation to intestinal microbiota and NAFLD development is limited. Here, we determined TLR expression patterns in peripheral blood mononuclear cells (PBMCs) of NAFLD patients and controls, their relation to intestinal microbiota and the impact of TLRs found altered in NAFLD development. Markers of intestinal permeability in blood and TLR mRNA expression in PBMCs were determined in 37 NAFLD patients and 15 age-matched healthy controls. Fecal microbiota composition was evaluated in 21 NAFLD patients and 9 controls using 16S rRNA gene amplicon sequencing. Furthermore, TLR1 −/− and C57BL/6 mice (n = 5–6/group) were pair-fed a liquid control or a fat-, fructose- and cholesterol-rich diet. Intestinal microbiota composition and markers of intestinal permeability like zonulin and bacterial endotoxin differed significantly between groups with the latter markers being significantly higher in NAFLD patients. Expression of TLR1-8 and 10 mRNA was detectable in PBMCs; however, only TLR1 expression, being higher in NAFLD patients, were significantly positively correlated with the prevalence of Holdemanella genus while negative correlations were found with Gemmiger and Ruminococcus genera. TLR1 −/− mice were significantly protected from the development of diet-induced NAFLD when compared to wild-type mice. While intestinal microbiota composition and permeability differed significantly between NAFLD patients and healthy subjects, in PBMCs, only TLR1 expression differed between groups. Still, targeting these alterations might be a beneficial approach in the treatment of NAFLD in some patients.Anja BaumannAnika NierAngélica Hernández-ArriagaAnnette BrandtMaria J. Lorenzo PisarelloCheng J. JinEsther PilarAmélia Camarinha-SilvaJörn M. SchattenbergIna BergheimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anja Baumann Anika Nier Angélica Hernández-Arriaga Annette Brandt Maria J. Lorenzo Pisarello Cheng J. Jin Esther Pilar Amélia Camarinha-Silva Jörn M. Schattenberg Ina Bergheim Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease
description	Abstract Toll-like receptors (TLRs) in the liver compartment have repeatedly been attributed to the development of non-alcoholic fatty liver disease (NAFLD). Knowledge on TLR expression in blood cells and their relation to intestinal microbiota and NAFLD development is limited. Here, we determined TLR expression patterns in peripheral blood mononuclear cells (PBMCs) of NAFLD patients and controls, their relation to intestinal microbiota and the impact of TLRs found altered in NAFLD development. Markers of intestinal permeability in blood and TLR mRNA expression in PBMCs were determined in 37 NAFLD patients and 15 age-matched healthy controls. Fecal microbiota composition was evaluated in 21 NAFLD patients and 9 controls using 16S rRNA gene amplicon sequencing. Furthermore, TLR1 −/− and C57BL/6 mice (n = 5–6/group) were pair-fed a liquid control or a fat-, fructose- and cholesterol-rich diet. Intestinal microbiota composition and markers of intestinal permeability like zonulin and bacterial endotoxin differed significantly between groups with the latter markers being significantly higher in NAFLD patients. Expression of TLR1-8 and 10 mRNA was detectable in PBMCs; however, only TLR1 expression, being higher in NAFLD patients, were significantly positively correlated with the prevalence of Holdemanella genus while negative correlations were found with Gemmiger and Ruminococcus genera. TLR1 −/− mice were significantly protected from the development of diet-induced NAFLD when compared to wild-type mice. While intestinal microbiota composition and permeability differed significantly between NAFLD patients and healthy subjects, in PBMCs, only TLR1 expression differed between groups. Still, targeting these alterations might be a beneficial approach in the treatment of NAFLD in some patients.
format	article
author	Anja Baumann Anika Nier Angélica Hernández-Arriaga Annette Brandt Maria J. Lorenzo Pisarello Cheng J. Jin Esther Pilar Amélia Camarinha-Silva Jörn M. Schattenberg Ina Bergheim
author_facet	Anja Baumann Anika Nier Angélica Hernández-Arriaga Annette Brandt Maria J. Lorenzo Pisarello Cheng J. Jin Esther Pilar Amélia Camarinha-Silva Jörn M. Schattenberg Ina Bergheim
author_sort	Anja Baumann
title	Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease
title_short	Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease
title_full	Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease
title_fullStr	Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease
title_full_unstemmed	Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease
title_sort	toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4bf6f872572040e897d0b276027d7f17
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Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease

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