| First Author | Zhang M | Year | 2018 |
| Journal | Dig Liver Dis | Volume | 50 |
| Issue | 10 | Pages | 1068-1075 |
| PubMed ID | 29730159 | Mgi Jnum | J:292659 |
| Mgi Id | MGI:6449919 | Doi | 10.1016/j.dld.2018.04.009 |
| Citation | Zhang M, et al. (2018) FXR deletion in hepatocytes does not affect the severity of alcoholic liver disease in mice. Dig Liver Dis 50(10):1068-1075 |
| abstractText | Emerging evidence has shown that FXR activation ameliorates the development of alcoholic liver diseases (ALD) while whole-body deficiency of FXR in mice leads to more severe ALD. However, it's unknown whether the enhanced susceptibility to ALD development in FXR(-/-) mice is due to deficiency of hepatic FXR or increased toxicity secondary to increased bile acid (BA) levels. Hepatocyte-specific FXR knockout mice (FXR(hep-/-)) present similar BA levels compared to wild-type mice, and are therefore a useful model to study a direct role of hepatic FXR in ALD development. FXR(hep-/-) mice were subject to an ALD model with chronic plus binge drinking of alcohol to determine the effects of hepatic FXR deficiency on ALD development. The FXR(hep-/-) mice showed an altered expression of genes involved in BA and lipid homeostasis with alcohol treatment. Despite a slightly increased trend in hepatic lipid deposition and collagen accumulation in FXR(hep-/-) mice, there were no significant differences in the severity of steatosis, inflammation, or fibrosis between WT and FXR(hep-/-) mice. Therefore, these findings indicate that FXR deficiency in hepatocytes might only play a minor role in ALD development. Deficiency of FXR in other non-hepatic tissues and/or increased BA levels resultant from whole-body FXR deficiency might be responsible for more severe ALD development. |
