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

Autor(en)

Anja Baumann, Anika Nier, Angélica Hernández-Arriaga, Annette Brandt, Maria José Lorenzo Pisarello, Amelia Camarinha-Silva, Cheng Jun Jin, Esther Pilar, Jörn M. Schattenberg, Ina Bergheim

Abstrakt

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.

Organisation(en)

Department für Ernährungswissenschaften

Externe Organisation(en)

Universität Hohenheim, Friedrich-Schiller-Universität Jena, Johannes Gutenberg-Universität Mainz, Universität Wien

Journal

Scientific Reports

Band

11

Anzahl der Seiten

15

ISSN

2045-2322

DOI

https://doi.org/10.1038/s41598-021-97346-9

Publikationsdatum

09-2021

Peer-reviewed

Ja

ÖFOS 2012

303009 Ernährungswissenschaften

Schlagwörter

ASJC Scopus Sachgebiete

General

Link zum Portal

https://ucris.univie.ac.at/portal/de/publications/tolllike-receptor-1-as-a-possible-target-in-nonalcoholic-fatty-liver-disease(7c09cb7a-7761-40ec-82ba-67e39fe700e1).html