Colesevelam Reduces Ethanol-Induced Liver Steatosis in Humanized Gnotobiotic Mice
| Autor: | Dennis Yamashita, Cristina Llorente, Patrick Stern, Noemí Cabré, Mary Conrad, Bernd Schnabl, Yi Duan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
CYP7A1 medicine.medical_specialty Alcoholic liver disease alcoholic liver disease bile acids microbiome QH301-705.5 medicine.drug_class Colesevelam Hydrochloride Alcoholic hepatitis Cholesterol 7 alpha-hydroxylase Article Mice 03 medical and health sciences Liver disease 0302 clinical medicine Bile acid sequestrant Internal medicine medicine Animals Germ-Free Life Biology (General) Cholesterol 7-alpha-Hydroxylase Liver injury Ethanol Colesevelam business.industry General Medicine medicine.disease Fatty Liver 030104 developmental biology Endocrinology Humanized mouse Female 030211 gastroenterology & hepatology business medicine.drug |
| Zdroj: | Cells; Volume 10; Issue 6; Pages: 1496 Cells, Vol 10, Iss 1496, p 1496 (2021) Cells |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10061496 |
| Popis: | Alcohol-related liver disease is associated with intestinal dysbiosis. Functional changes in the microbiota affect bile acid metabolism and result in elevated serum bile acids in patients with alcohol-related liver disease. The aim of this study was to identify the potential role of the bile acid sequestrant colesevelam in a humanized mouse model of ethanol-induced liver disease. We colonized germ-free (GF) C57BL/6 mice with feces from patients with alcoholic hepatitis and subjected humanized mice to the chronic–binge ethanol feeding model. Ethanol-fed gnotobiotic mice treated with colesevelam showed reduced hepatic levels of triglycerides and cholesterol, but liver injury and inflammation were not decreased as compared with non-treated mice. Colesevelam reduced hepatic cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1) protein expression, although serum bile acids were not lowered. In conclusion, our findings indicate that colesevelam treatment mitigates ethanol-induced liver steatosis in mice. |
| Databáze: | OpenAIRE |
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