| Title: | 12 alpha-Hydroxylated bile acid induces hepatic steatosis with dysbiosis in rats |
| Authors: | Lee, Ja-Young Browse this author |
| Shimizu, Hidehisa Browse this author |
| Hagio, Masahito Browse this author |
| Fukiya, Satoru Browse this author |
| Watanabe, Masamichi Browse this author |
| Tanaka, Yasutake Browse this author |
| Joe, Ga-Hyun Browse this author |
| Iwaya, Hitoshi Browse this author |
| Yoshitsugu, Reika Browse this author |
| Kikuchi, Keidai Browse this author |
| Tsuji, Misaki Browse this author |
| Baba, Nanako Browse this author |
| Nose, Takuma Browse this author |
| Tada, Koji Browse this author |
| Hanai, Taketo Browse this author |
| Hori, Shota Browse this author |
| Takeuchi, Akari Browse this author |
| Furukawa, Yumiko Browse this author |
| Shirouchi, Bungo Browse this author |
| Sato, Masao Browse this author |
| Ooka, Tadasuke Browse this author |
| Ogura, Yoshitoshi Browse this author |
| Hayashi, Tetsuya Browse this author |
| Yokota, Atsushi Browse this author |
| Ishizuka, Satoshi Browse this author →KAKEN DB |
| Keywords: | Cholic acid |
| Deoxycholic acid |
| Dysbiosis |
| 4 beta-Hydroxycholesterol |
| Non-alcoholic fatty liver disease |
| Simple hepatic steatosis |
| Issue Date: | Dec-2020 |
| Publisher: | Elsevier |
| Journal Title: | Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids |
| Volume: | 1865 |
| Issue: | 12 |
| Start Page: | 158811 |
| Publisher DOI: | 10.1016/j.bbalip.2020.158811 |
| Abstract: | 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. |
| Rights: | http://creativecommons.org/licenses/BY-NC-ND/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/79988 |
| Appears in Collections: | 農学院・農学研究院 (Graduate School of Agriculture / Faculty of Agriculture) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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