12 alpha-Hydroxylated bile acid induces hepatic steatosis with dysbiosis in rats

Lee, Ja-Young; Shimizu, Hidehisa; Hagio, Masahito et al.

Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids, 2020, 1865(12), 158811

Permalink : https://hdl.handle.net/2115/79988

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論文情報

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アクセス権
open access
URI
https://hdl.handle.net/2115/79988
タイトル
12 alpha-Hydroxylated bile acid induces hepatic steatosis with dysbiosis in rats
著者
Lee, Ja-Young ; Shimizu, Hidehisa ; Hagio, Masahito ; Fukiya, Satoru ; Watanabe, Masamichi ; Tanaka, Yasutake ; Joe, Ga-Hyun ; Iwaya, Hitoshi ; Yoshitsugu, Reika ; Kikuchi, Keidai ; Tsuji, Misaki ; Baba, Nanako ; Nose, Takuma ; Tada, Koji ; Hanai, Taketo ; Hori, Shota ; Takeuchi, Akari ; Furukawa, Yumiko ; Shirouchi, Bungo ; Sato, Masao ; Ooka, Tadasuke ; Ogura, Yoshitoshi ; Hayashi, Tetsuya ; Yokota, Atsushi ; Ishizuka, Satoshi
著者名
Lee, Ja-Young
著者名
Shimizu, Hidehisa
著者名
Hagio, Masahito
著者名
Fukiya, Satoru
著者名
Watanabe, Masamichi
著者名
Tanaka, Yasutake
著者名
Joe, Ga-Hyun
著者名
Iwaya, Hitoshi
著者名
Yoshitsugu, Reika
著者名
Kikuchi, Keidai
著者名
Tsuji, Misaki
著者名
Baba, Nanako
著者名
Nose, Takuma
著者名
Tada, Koji
著者名
Hanai, Taketo
著者名
Hori, Shota
著者名
Takeuchi, Akari
著者名
Furukawa, Yumiko
著者名
Shirouchi, Bungo
著者名
Sato, Masao
著者名
Ooka, Tadasuke
著者名
Ogura, Yoshitoshi
著者名
Hayashi, Tetsuya
著者名
Yokota, Atsushi
e-Rad_Researcher
00271627
著者名
Ishizuka, Satoshi
言語
英語
キーワード
Cholic acid
Deoxycholic acid
Dysbiosis
4 beta-Hydroxycholesterol
Non-alcoholic fatty liver disease
Simple hepatic steatosis
発行日
2020-12
出版者
Elsevier
収録物名
Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids
巻(号)
1865(12)
ページ
158811
抄録
There is an increasing need to explore the mechanism of the progression of non-alcoholic fatty liver disease. Steroid metabolism is closely linked to hepatic steatosis and steroids are excreted as bile acids (BAs). Here, we demonstrated that feeding WKAH/HkmSlc inbred rats a diet supplemented with cholic acid (CA) at 0.5 g/kg for 13 weeks induced simple steatosis without obesity. Liver triglyceride and cholesterol levels were increased accompanied by mild elevation of aminotransferase activities. There were no signs of inflammation, insulin resistance, oxidative stress, or fibrosis. CA supplementation increased levels of CA and taurocholic acid (TCA) in enterohepatic circulation and deoxycholic acid (DCA) levels in cecum with an increased ratio of 12 alpha-hydroxylated BAs to non-12 alpha-hydroxylated BAs. Analyses of hepatic gene expression revealed no apparent feedback control of BA and cholesterol biosynthesis. CA feeding induced dysbiosis in cecal microbiota with enrichment of DCA producers, which underlines the increased cecal DCA levels. The mechanism of steatosis was increased expression of Srebp1 (positive regulator of liver lipogenesis) through activation of the liver X receptor by increased oxysterols in the CA-fed rats, especially 4 beta-hydroxycholesterol (4 beta OH) formed by upregulated expression of hepatic Cyp3a2, responsible for 4 beta OH formation. Multiple regression analyses identified portal TCA and cecal DCA as positive predictors for liver 4 beta OH levels. The possible mechanisms linking these predictors and upregulated expression of Cyp3a2 are discussed. Overall, our observations highlight the role of 12 alpha-hydroxylated BAs in triggering liver lipogenesis and allow us to explore the mechanisms of hepatic steatosis onset, focusing on cholesterol and BA metabolism.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
PISSN
1388-1981
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.1016/j.bbalip.2020.158811