Cargando…
Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet
Background: Recently, we established a novel rodent model of nonalcoholic steatohepatitis (NASH) with advanced fibrosis induced by a high-fat and high-cholesterol (HFC) diet containing cholic acid (CA), which is known to cause hepatotoxicity. The present study aimed to elucidate the direct impact of...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409005/ https://www.ncbi.nlm.nih.gov/pubmed/36012527 http://dx.doi.org/10.3390/ijms23169268 |
_version_ | 1784774743070605312 |
---|---|
author | Ichimura-Shimizu, Mayuko Watanabe, Shiro Kashirajima, Yuka Nagatomo, Ami Wada, Hitomi Tsuneyama, Koichi Omagari, Katsuhisa |
author_facet | Ichimura-Shimizu, Mayuko Watanabe, Shiro Kashirajima, Yuka Nagatomo, Ami Wada, Hitomi Tsuneyama, Koichi Omagari, Katsuhisa |
author_sort | Ichimura-Shimizu, Mayuko |
collection | PubMed |
description | Background: Recently, we established a novel rodent model of nonalcoholic steatohepatitis (NASH) with advanced fibrosis induced by a high-fat and high-cholesterol (HFC) diet containing cholic acid (CA), which is known to cause hepatotoxicity. The present study aimed to elucidate the direct impact of dietary CA on the progression of NASH induced by feeding the HFC diet. Methods: Nine-week-old male Sprague–Dawley rats were randomly assigned to receive a normal, HFC, or CA-supplemented (0.1%, 0.5% or 2.0%, w/w) HFC diet for 9 weeks. Results: Histopathological assessment revealed that the supplementation of CA dose-dependently aggravated hepatic steatosis, inflammation, and fibrosis, reaching stage 4 cirrhosis in the 2.0% CA diet group. In contrast, the rats that were fed the HFC diet without any added CA developed mild steatosis and inflammation without fibrosis. The hepatic cholesterol content and mRNA expression involved in inflammatory response and fibrogenesis was higher in a CA dose-dependent manner. The hepatic chenodeoxycholic acid levels were higher in 2.0% CA diet group than in the control, although hepatic levels of total bile acid and CA did not increase dose-dependently with CA intake. Conclusion: Adding CA to the HFC diet altered bile acid metabolism and inflammatory response and triggered the development of fibrosis in the rat liver. |
format | Online Article Text |
id | pubmed-9409005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94090052022-08-26 Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet Ichimura-Shimizu, Mayuko Watanabe, Shiro Kashirajima, Yuka Nagatomo, Ami Wada, Hitomi Tsuneyama, Koichi Omagari, Katsuhisa Int J Mol Sci Article Background: Recently, we established a novel rodent model of nonalcoholic steatohepatitis (NASH) with advanced fibrosis induced by a high-fat and high-cholesterol (HFC) diet containing cholic acid (CA), which is known to cause hepatotoxicity. The present study aimed to elucidate the direct impact of dietary CA on the progression of NASH induced by feeding the HFC diet. Methods: Nine-week-old male Sprague–Dawley rats were randomly assigned to receive a normal, HFC, or CA-supplemented (0.1%, 0.5% or 2.0%, w/w) HFC diet for 9 weeks. Results: Histopathological assessment revealed that the supplementation of CA dose-dependently aggravated hepatic steatosis, inflammation, and fibrosis, reaching stage 4 cirrhosis in the 2.0% CA diet group. In contrast, the rats that were fed the HFC diet without any added CA developed mild steatosis and inflammation without fibrosis. The hepatic cholesterol content and mRNA expression involved in inflammatory response and fibrogenesis was higher in a CA dose-dependent manner. The hepatic chenodeoxycholic acid levels were higher in 2.0% CA diet group than in the control, although hepatic levels of total bile acid and CA did not increase dose-dependently with CA intake. Conclusion: Adding CA to the HFC diet altered bile acid metabolism and inflammatory response and triggered the development of fibrosis in the rat liver. MDPI 2022-08-17 /pmc/articles/PMC9409005/ /pubmed/36012527 http://dx.doi.org/10.3390/ijms23169268 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ichimura-Shimizu, Mayuko Watanabe, Shiro Kashirajima, Yuka Nagatomo, Ami Wada, Hitomi Tsuneyama, Koichi Omagari, Katsuhisa Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet |
title | Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet |
title_full | Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet |
title_fullStr | Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet |
title_full_unstemmed | Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet |
title_short | Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet |
title_sort | dietary cholic acid exacerbates liver fibrosis in nash model of sprague–dawley rats fed a high-fat and high-cholesterol diet |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409005/ https://www.ncbi.nlm.nih.gov/pubmed/36012527 http://dx.doi.org/10.3390/ijms23169268 |
work_keys_str_mv | AT ichimurashimizumayuko dietarycholicacidexacerbatesliverfibrosisinnashmodelofspraguedawleyratsfedahighfatandhighcholesteroldiet AT watanabeshiro dietarycholicacidexacerbatesliverfibrosisinnashmodelofspraguedawleyratsfedahighfatandhighcholesteroldiet AT kashirajimayuka dietarycholicacidexacerbatesliverfibrosisinnashmodelofspraguedawleyratsfedahighfatandhighcholesteroldiet AT nagatomoami dietarycholicacidexacerbatesliverfibrosisinnashmodelofspraguedawleyratsfedahighfatandhighcholesteroldiet AT wadahitomi dietarycholicacidexacerbatesliverfibrosisinnashmodelofspraguedawleyratsfedahighfatandhighcholesteroldiet AT tsuneyamakoichi dietarycholicacidexacerbatesliverfibrosisinnashmodelofspraguedawleyratsfedahighfatandhighcholesteroldiet AT omagarikatsuhisa dietarycholicacidexacerbatesliverfibrosisinnashmodelofspraguedawleyratsfedahighfatandhighcholesteroldiet |