Citrulline supplementation attenuates the development of non-alcoholic steatohepatitis in female mice through mechanisms involving intestinal arginase
| العنوان: | Citrulline supplementation attenuates the development of non-alcoholic steatohepatitis in female mice through mechanisms involving intestinal arginase |
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| المؤلفون: | Anika Nier, Ina Bergheim, Amélia Camarinha-Silva, Cheng Jun Jin, Annette Brandt, Anja Baumann, Angélica Hernández-Arriaga, Dragana Rajcic, Victor Sánchez, Finn Jung |
| المصدر: | Redox Biology Redox Biology, Vol 41, Iss, Pp 101879-(2021) |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Medicine (General), F, fructose, Arginine, Clinical Biochemistry, AST, aspartate aminotransferase, Biochemistry, Mice, AUC, area under the curve, NOHA, N(ω)-hydroxy-nor-l-arginine, Liver disease, chemistry.chemical_compound, PCR, polymerase chain reaction, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, ARG2, arginase 2, 3-NT, 3-nitrotyrosine, Citrulline, Biology (General), NAS, NAFLD activity score, Fatty liver, FFC, fat-, fructose- and cholesterol-rich diet, L-Cit, l-citrulline, Arginase, medicine.anatomical_structure, Liver, iNOS, inducible nitric oxide synthase, Female, Research Paper, NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, QH301-705.5, C, control diet, NASH, non-alcoholic steatohepatitis, TNFα, tumor necrosis factor alpha, Intestinal permeability, Diet, High-Fat, SEM, standard error of the mean, NO, 03 medical and health sciences, R5-920, Tlr4, toll-like receptor 4, 4-HNE, 4-hydroxynonenal, ALT, alanine aminotransferase, Internal medicine, medicine, Animals, Hepatic inflammation, Gpr41, G-protein-coupled receptor 41, NO, nitric oxide, business.industry, Bacterial endotoxin, Organic Chemistry, E%, percentage of energy, medicine.disease, ZO-1, zonula occludens 1, Small intestine, GTT, glucose-tolerance-test, Mice, Inbred C57BL, Toll-Like Receptor 4, 030104 developmental biology, Endocrinology, chemistry, Dietary Supplements, Myd88, myeloid differentiation primary response 88, Gpr43, G-protein-coupled receptor 43, Steatohepatitis, business, 030217 neurology & neurosurgery |
| الوصف: | 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. Graphical abstract Image 1 Highlights • l-citrulline diminished progression of non-alcoholic fatty liver disease (NAFLD). • l-citrulline protects from fructose-induced small intestinal barrier dysfunction. • NASH development is associated with a loss of arginase activity in small intestine. • l-citrulline improves intestinal arginase activity in diet-induced NAFLD. • Arginase inhibitor attenuates effects of l-citrulline on NAFLD development. |
| وصف الملف: | application/pdf |
| تدمد: | 2213-2317 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62c29ebb68a39a4a69ad56089e73e70eTest https://doi.org/10.1016/j.redox.2021.101879Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....62c29ebb68a39a4a69ad56089e73e70e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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