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Enhanced Alcoholic Liver Disease in Mice with Intestine-specific Farnesoid X Receptor Deficiency
Alcoholic fatty liver disease (AFLD) is one of the major causes of liver morbidity and mortality worldwide. We have previously shown that whole-body, but not hepatocyte-specific, deficiency of farnesoid X receptor (FXR) in mice worsens AFLD, suggesting that extra-hepatic FXR deficiency is critical f...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487140/ https://www.ncbi.nlm.nih.gov/pubmed/32404932 http://dx.doi.org/10.1038/s41374-020-0439-y |
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author | Huang, Mingxing Kong, Bo Zhang, Min Rizzolo, Daniel Armstrong, Laura E. Schumacher, Justin D. Chow, Monica D. Lee, Yi-Horng Joseph, Laurie B. Stofan, Mary Zhang, Lanjing Guo, Grace L |
author_facet | Huang, Mingxing Kong, Bo Zhang, Min Rizzolo, Daniel Armstrong, Laura E. Schumacher, Justin D. Chow, Monica D. Lee, Yi-Horng Joseph, Laurie B. Stofan, Mary Zhang, Lanjing Guo, Grace L |
author_sort | Huang, Mingxing |
collection | PubMed |
description | Alcoholic fatty liver disease (AFLD) is one of the major causes of liver morbidity and mortality worldwide. We have previously shown that whole-body, but not hepatocyte-specific, deficiency of farnesoid X receptor (FXR) in mice worsens AFLD, suggesting that extra-hepatic FXR deficiency is critical for AFLD development. Intestinal FXR is critical in suppressing hepatic bile acid (BA) synthesis by inducing fibroblast growth factor 15 (FGF15) in mice and FGF19 in humans. We hypothesized that intestinal FXR is critical for reducing AFLD development in mice. To test this hypothesis, we compared the AFLD severity in wild type (WT) and intestine-specific Fxr knockout (FXR(Int−/−)) mice following treatment with control or ethanol-containing diet. We found that FXR(Int−/−) mice were more susceptible to ethanol-induced liver steatosis and inflammation, compared to WT mice. Ethanol treatment altered the expression of hepatic genes involved in lipid and bile acid homeostasis, and ethanol detoxification. Gut FXR deficiency increased intestinal permeability, likely due to reduced mucosal integrity, as revealed by decreased secretion of Mucin 2 protein and lower levels of E-cadherin protein. In summary, intestinal FXR may protect AFLD development by maintaining gut integrity. |
format | Online Article Text |
id | pubmed-8487140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-84871402021-10-02 Enhanced Alcoholic Liver Disease in Mice with Intestine-specific Farnesoid X Receptor Deficiency Huang, Mingxing Kong, Bo Zhang, Min Rizzolo, Daniel Armstrong, Laura E. Schumacher, Justin D. Chow, Monica D. Lee, Yi-Horng Joseph, Laurie B. Stofan, Mary Zhang, Lanjing Guo, Grace L Lab Invest Article Alcoholic fatty liver disease (AFLD) is one of the major causes of liver morbidity and mortality worldwide. We have previously shown that whole-body, but not hepatocyte-specific, deficiency of farnesoid X receptor (FXR) in mice worsens AFLD, suggesting that extra-hepatic FXR deficiency is critical for AFLD development. Intestinal FXR is critical in suppressing hepatic bile acid (BA) synthesis by inducing fibroblast growth factor 15 (FGF15) in mice and FGF19 in humans. We hypothesized that intestinal FXR is critical for reducing AFLD development in mice. To test this hypothesis, we compared the AFLD severity in wild type (WT) and intestine-specific Fxr knockout (FXR(Int−/−)) mice following treatment with control or ethanol-containing diet. We found that FXR(Int−/−) mice were more susceptible to ethanol-induced liver steatosis and inflammation, compared to WT mice. Ethanol treatment altered the expression of hepatic genes involved in lipid and bile acid homeostasis, and ethanol detoxification. Gut FXR deficiency increased intestinal permeability, likely due to reduced mucosal integrity, as revealed by decreased secretion of Mucin 2 protein and lower levels of E-cadherin protein. In summary, intestinal FXR may protect AFLD development by maintaining gut integrity. 2020-05-13 2020-09 /pmc/articles/PMC8487140/ /pubmed/32404932 http://dx.doi.org/10.1038/s41374-020-0439-y Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Huang, Mingxing Kong, Bo Zhang, Min Rizzolo, Daniel Armstrong, Laura E. Schumacher, Justin D. Chow, Monica D. Lee, Yi-Horng Joseph, Laurie B. Stofan, Mary Zhang, Lanjing Guo, Grace L Enhanced Alcoholic Liver Disease in Mice with Intestine-specific Farnesoid X Receptor Deficiency |
title | Enhanced Alcoholic Liver Disease in Mice with Intestine-specific Farnesoid X Receptor Deficiency |
title_full | Enhanced Alcoholic Liver Disease in Mice with Intestine-specific Farnesoid X Receptor Deficiency |
title_fullStr | Enhanced Alcoholic Liver Disease in Mice with Intestine-specific Farnesoid X Receptor Deficiency |
title_full_unstemmed | Enhanced Alcoholic Liver Disease in Mice with Intestine-specific Farnesoid X Receptor Deficiency |
title_short | Enhanced Alcoholic Liver Disease in Mice with Intestine-specific Farnesoid X Receptor Deficiency |
title_sort | enhanced alcoholic liver disease in mice with intestine-specific farnesoid x receptor deficiency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487140/ https://www.ncbi.nlm.nih.gov/pubmed/32404932 http://dx.doi.org/10.1038/s41374-020-0439-y |
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