Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male <i>Cyp2c70</i> Knockout Mice
<i>Cyp2c70</i> knockout mice lack the enzyme that produces muricholic acids and show a “human-like” hydrophobic bile acid pool-induced hepatobiliary injury. In this study, we investigated the potential anti-cholestasis effect of glycine-conjugated β muricholic acid (G-β-MCA) in male <...
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MDPI AG
2023-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/10/1371 |
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| author | Mohammad Nazmul Hasan Jianglei Chen Huaiwen Wang Yanhong Du Yung Dai Clayton Lijie Gu Tiangang Li |
| author_facet | Mohammad Nazmul Hasan Jianglei Chen Huaiwen Wang Yanhong Du Yung Dai Clayton Lijie Gu Tiangang Li |
| author_sort | Mohammad Nazmul Hasan |
| collection | DOAJ |
| description | <i>Cyp2c70</i> knockout mice lack the enzyme that produces muricholic acids and show a “human-like” hydrophobic bile acid pool-induced hepatobiliary injury. In this study, we investigated the potential anti-cholestasis effect of glycine-conjugated β muricholic acid (G-β-MCA) in male <i>Cyp2c70</i> KO mice based on its hydrophilic physiochemical property and signaling property as an farnesoid X receptor (FXR) antagonist. Our results showed that G-β-MCA treatment for 5 weeks alleviated ductular reaction and liver fibrosis and improved gut barrier function. Analysis of bile acid metabolism suggested that exogenously administered G-β-MCA was poorly absorbed in the small intestine and mostly deconjugated in the large intestine and converted to taurine-conjugated MCA (T-MCA) in the liver, leading to T-MCA enrichment in the bile and small intestine. These changes decreased the biliary and intestine bile acid hydrophobicity index. Furthermore, G-β-MCA treatment decreased intestine bile acid absorption via unknown mechanisms, resulting in increased fecal bile acid excretion and a reduction in total bile acid pool size. In conclusion, G-β-MCA treatment reduces the bile acid pool size and hydrophobicity and improves liver fibrosis and gut barrier function in <i>Cyp2c70</i> KO mice. |
| first_indexed | 2024-03-11T03:51:18Z |
| format | Article |
| id | doaj.art-0057211fb2294a19860c3bdebc5e0b6b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:51:18Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-0057211fb2294a19860c3bdebc5e0b6b2023-11-18T00:52:36ZengMDPI AGCells2073-44092023-05-011210137110.3390/cells12101371Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male <i>Cyp2c70</i> Knockout MiceMohammad Nazmul Hasan0Jianglei Chen1Huaiwen Wang2Yanhong Du3Yung Dai Clayton4Lijie Gu5Tiangang Li6Harold Hamm Diabetes Center, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAHarold Hamm Diabetes Center, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USALaboratory for Molecular Biology and Cytometry Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAHarold Hamm Diabetes Center, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAHarold Hamm Diabetes Center, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAHarold Hamm Diabetes Center, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAHarold Hamm Diabetes Center, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA<i>Cyp2c70</i> knockout mice lack the enzyme that produces muricholic acids and show a “human-like” hydrophobic bile acid pool-induced hepatobiliary injury. In this study, we investigated the potential anti-cholestasis effect of glycine-conjugated β muricholic acid (G-β-MCA) in male <i>Cyp2c70</i> KO mice based on its hydrophilic physiochemical property and signaling property as an farnesoid X receptor (FXR) antagonist. Our results showed that G-β-MCA treatment for 5 weeks alleviated ductular reaction and liver fibrosis and improved gut barrier function. Analysis of bile acid metabolism suggested that exogenously administered G-β-MCA was poorly absorbed in the small intestine and mostly deconjugated in the large intestine and converted to taurine-conjugated MCA (T-MCA) in the liver, leading to T-MCA enrichment in the bile and small intestine. These changes decreased the biliary and intestine bile acid hydrophobicity index. Furthermore, G-β-MCA treatment decreased intestine bile acid absorption via unknown mechanisms, resulting in increased fecal bile acid excretion and a reduction in total bile acid pool size. In conclusion, G-β-MCA treatment reduces the bile acid pool size and hydrophobicity and improves liver fibrosis and gut barrier function in <i>Cyp2c70</i> KO mice.https://www.mdpi.com/2073-4409/12/10/1371bile acidASBTCYP7A1FXRcholestasisCYP2C70 |
| spellingShingle | Mohammad Nazmul Hasan Jianglei Chen Huaiwen Wang Yanhong Du Yung Dai Clayton Lijie Gu Tiangang Li Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male <i>Cyp2c70</i> Knockout Mice Cells bile acid ASBT CYP7A1 FXR cholestasis CYP2C70 |
| title | Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male <i>Cyp2c70</i> Knockout Mice |
| title_full | Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male <i>Cyp2c70</i> Knockout Mice |
| title_fullStr | Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male <i>Cyp2c70</i> Knockout Mice |
| title_full_unstemmed | Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male <i>Cyp2c70</i> Knockout Mice |
| title_short | Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male <i>Cyp2c70</i> Knockout Mice |
| title_sort | glycine β muricholic acid improves liver fibrosis and gut barrier function by reducing bile acid pool size and hydrophobicity in male i cyp2c70 i knockout mice |
| topic | bile acid ASBT CYP7A1 FXR cholestasis CYP2C70 |
| url | https://www.mdpi.com/2073-4409/12/10/1371 |
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