کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5508361 | 1537687 | 2017 | 41 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: Novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease
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کلمات کلیدی
BPASREBF1NAFLDFatty acid - اسید چربbisphenol A (BPA) - بیسفنول A (BPA)Bisphenol A - بیسفنول ای، بیسفنول ANonalcoholic fatty liver disease (NAFLD) - بیماری کبدی چرب غیر الکلی (NAFLD)Nonalcoholic fatty liver disease - بیماری کبدی چربی غیر الکلیLipid accumulation - تجمع لیپیدtriglyceride - تریگلیسریدSteatosis - تغییر چرب یا استئاتوز Insulin resistance - مقاومت به انسولینMicroRNA - میکرو RNA MiRNA - میکروRNA، ریزآرانای، miRNAsterol regulatory element-binding protein 1 - پروتئین اتصال دهنده عصاره استرول 1total cholesterol - کلسترول تام
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Exposure to Bisphenol A (BPA) has been associated with the development of nonalcoholic fatty liver disease (NAFLD) but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study was designed to explore whether exposure to BPA-triggered abnormal steatosis and lipid accumulation in the liver could be modulated by miR-192. We showed that male post-weaning C57BL/6 mice exposed to 50 μg/kg/day of BPA by oral gavage for 90 days displayed a NAFLD-like phenotype. In addition, we found in mouse liver and human HepG2 cells that BPA-induced hepatic steatosis and lipid accumulation were associated with decreased expression of miR-192, upregulation of SREBF1 and a series of genes involved in de novo lipogenesis. Downregulation of miR-192 in BPA-exposed hepatocytes could be due to defective pre-miR-192 processing by DROSHA. Using HepG2 cells, we further confirmed that miR-192 directly acted on the 3â²UTR of SREBF1, contributing to dysregulation of lipid homeostasis in hepatocytes. MiR-192 mimic and lentivirus-mediated overexpression of miR-192 improved BPA-induced hepatic steatosis by suppressing SREBF1. Lastly, we noted that lipid accumulation was not a strict requirement for developing insulin resistance in mice after BPA treatment. In conclusion, this study demonstrated a novel mechanism in which NAFLD associated with BPA exposure arose from alterations in the miR-192-SREBF1 axis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1862, Issue 9, September 2017, Pages 869-882
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1862, Issue 9, September 2017, Pages 869-882
نویسندگان
Yi Lin, Dongxiao Ding, Qiansheng Huang, Qiong Liu, Haoyang Lu, Yanyang Lu, Yulang Chi, Xia Sun, Guozhu Ye, Huimin Zhu, Jie Wei, Sijun Dong,