Citrulline supplementation attenuates the development of non-alcoholic steatohepatitis in female mice through mechanisms involving intestinal arginase

Autor(en)
Dragana Rajcic, Angélica Hernández-Arriaga, Annette Brandt, Anika Nier, Cheng Jun Jin, Victor Manuel Sanchez Juarez, Finn Jung, Amélia Camarinha Silva, Anja Baumann, Ina Bergheim
Abstrakt

Non-alcoholic fatty liver disease (NAFLD) is by now the most prevalent liver disease worldwide. The non-proteogenic amino acid l-citrulline (L-Cit) has been shown to protect mice from the development of NAFLD. Here, we aimed to further assess if L-Cit also attenuates the progression of a pre-existing diet-induced NAFLD and to determine molecular mechanisms involved. Female C57BL/6J mice were either fed a liquid fat-, fructose- and cholesterol-rich diet (FFC) or control diet (C) for 8 weeks to induce early stages of NASH followed by 5 more weeks with either FFC-feeding +/- 2.5 g L-Cit/kg bw or C-feeding. In addition, female C57BL/6J mice were either pair-fed a FFC +/- 2.5 g L-Cit/kg bw +/- 0.01 g/kg bw i.p. N(ω)-hydroxy-nor-l-arginine (NOHA) or C diet for 8 weeks.

The protective effects of supplementing L-Cit on the progression of a pre-existing NAFLD were associated with an attenuation of 1) the increased translocation of bacterial endotoxin and 2) the loss of tight junction proteins as well as 3) arginase activity in small intestinal tissue, while no marked changes in intestinal microbiota composition were prevalent in small intestine. Treatment of mice with the arginase inhibitor NOHA abolished the protective effects of L-Cit on diet-induced NAFLD. Our results suggest that the protective effects of L-Cit on the development and progression of NAFLD are related to alterations of intestinal arginase activity and intestinal permeability.

Organisation(en)
Department für Ernährungswissenschaften
Externe Organisation(en)
Universität Hohenheim, Friedrich-Schiller-Universität Jena
Journal
Redox biology
Band
41
Anzahl der Seiten
12
DOI
https://doi.org/10.1016/j.redox.2021.101879
Publikationsdatum
05-2021
Peer-reviewed
Ja
ÖFOS 2012
303009 Ernährungswissenschaften
Schlagwörter
ASJC Scopus Sachgebiete
Clinical Biochemistry, Organic Chemistry
Link zum Portal
https://ucris.univie.ac.at/portal/de/publications/citrulline-supplementation-attenuates-the-development-of-nonalcoholic-steatohepatitis-in-female-mice-through-mechanisms-involving-intestinal-arginase(8f8a4bae-1d13-4f2d-887a-c7efbabb667f).html