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
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
غدد درون ریز، دیابت و متابولیسم
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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 FXRâ/â mice is due to deficiency of hepatic FXR or increased toxicity secondary to increased bile acid (BA) levels. Hepatocyte-specific FXR knockout mice (FXRhepâ/â) 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. FXRhepâ/â 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 FXRhepâ/â 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 FXRhepâ/â mice, there were no significant differences in the severity of steatosis, inflammation, or fibrosis between WT and FXRhepâ/â 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
Journal: Digestive and Liver Disease - Volume 50, Issue 10, October 2018, Pages 1068-1075
نویسندگان
Min Zhang, Bo Kong, Mingxing Huang, Ruixuan Wan, Laura E. Armstrong, Justin D. Schumacher, Daniel Rizzolo, Monica D. Chow, Yi-Horng Lee, Grace L Guo,