کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
11018674 1719086 2018 28 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
FXR deletion in hepatocytes does not affect the severity of alcoholic liver disease in mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی غدد درون ریز، دیابت و متابولیسم
پیش نمایش صفحه اول مقاله
FXR deletion in hepatocytes does not affect the severity of alcoholic liver disease in mice
چکیده انگلیسی
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 (FXRhep−/−) 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. FXRhep−/− 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 FXRhep−/− 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 FXRhep−/− mice, there were no significant differences in the severity of steatosis, inflammation, or fibrosis between WT and FXRhep−/− 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Digestive and Liver Disease - Volume 50, Issue 10, October 2018, Pages 1068-1075
نویسندگان
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