直近一年間の累計
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ID 117819
著者
Watanabe, Shiro University of Toyama
Kashirajima, Yuka University of Nagasaki
Nagatomo, Ami University of Nagasaki
Wada, Hitomi University of Nagasaki
Omagari, Katsuhisa University of Nagasaki
キーワード
cholic acid
liver fibrosis
nonalcoholic steatohepatitis
high-fat and high-cholesterol diet
Sprague–Dawley rat
bile acid
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
International Journal of Molecular Sciences
ISSN
14220067
出版者
MDPI
23
16
開始ページ
9268
発行日
2022-08-17
権利情報
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/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系