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Cited by 16Drug Transport and Resistance MechanismsLiver physiology and pathologyDrug-Induced Hepatotoxicity and Protection

Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male Cyp2c70 Knockout Mice

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Hasan, Mohammad Nazmul, Chen, Jianglei, Wang, Huaiwen, Du, Yanhong, Clayton, Yung Dai, Gu, Lijie, Li, Tiangang·2023·Cells
DOI 10.3390/cells12101371PMC PMC10216635
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Abstract

Cyp2c70 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 Cyp2c70 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 Cyp2c70 KO mice.

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References 31 · Cited by 16

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Authors
Hasan, M. N., Chen, J., Wang, H., Du, Y., Clayton, Y. D., Gu, L., & Li, T.
Affiliations
University of Oklahoma Health Sciences Center (US)
Corresponding author
Li, Tiangang
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2023-05-12
Volume
12
Issue
10
Pages
1371
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells12101371
PMC
PMC10216635
OpenAlex
W4376275123
Cited by
16
References
31
Citations by year
2026: 6 · 2025: 5 · 2024: 4 · 2023: 1
FWCI
1.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
NIH (1R01DK131064-01, 1R01 DK117965-01A1)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
liver fibrosis, intestinal barrier, bile acid pool size, bile acid metabolism, intestinal bile acid absorption, fecal bile acid excretion, ductular reaction, hepatobiliary injury
MeSH terms
Animals, Bile Acids and Salts, Cholic Acids, Glycine, Humans, Liver Cirrhosis, Male, Mice, Knockout, Mice

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