کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6104966 1211143 2013 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ArticlePharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice
ترجمه فارسی عنوان
تحقیقات در مورد مهار بازدارندگی اسید چرب اسید چرب آدیوسیت باعث کاهش آسیب شدید کبدی و استئاتوهپاتیت غیر الکلی در موش می شود
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
چکیده انگلیسی

Background & AimsAdipocyte fatty acid binding protein (A-FABP) is a key mediator of inflammatory response in macrophages. Increased hepatic expression and circulating levels of A-FABP have been observed in patients with non-alcoholic fatty liver disease (NAFLD). Here, we investigated the role of A-FABP in both lipopolysaccaride (LPS)-induced acute liver injury and high fat high cholesterol (HFHC) diet-induced NAFLD in mice.MethodsMice with LPS-induced acute liver injury and HFHC diet-induced obesity were treated with the A-FABP inhibitor BMS309403. Liver tissues of the mice were analyzed by immunohistochemistry, Western blot or real-time PCR.ResultsA-FABP expression in Kupffer cells was significantly elevated in mice with LPS-induced acute liver injury and HFHC diet-induced obesity, as compared to their healthy controls. Pretreatment of mice with BMS309403 led to a diminished LPS-induced elevation in serum levels of alanine transaminase and hepatic production of pro-inflammatory cytokines. Likewise, chronic treatment of HFHC diet-induced obese mice with BMS309403 ameliorated hepatic steatosis, macrophage infiltration, and cellular ballooning of hepatocytes. Such improvements in liver function and morphology were accompanied by significantly decreased activation of both c-Jun and NF-κB. Pretreatment with BMS309403 suppressed both LPS- and palmitate-induced pro-inflammatory responses in isolated rat Kupffer cells. Adenovirus-mediated ectopic expression of A-FABP alone was sufficient to induce liver injury and inflammation in mice.ConclusionsThese findings suggest that A-FABP is an important contributor to both LPS-induced acute liver injury and diet-induced NAFLD by potentiating inflammation in Kupffer cells. Pharmacological inhibition of A-FABP may represent a promising modality for obesity-related non-alcoholic steatohepatitis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 58, Issue 2, February 2013, Pages 358-364
نویسندگان
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