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Lipid accumulation was examined by Filipin staining and intracellular cholesterol quantitative assay. The gene and protein expression of molecules involved in RAS and low\u2010density lipoprotein receptor (LDLr) pathway was examined by real\u2010time PCR, immunofluorescent staining and Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was significantly increased expression of RAS components and extracellular matrix (ECM) in livers of high\u2010fat\u2010diet\u2010fed apolipoprotein E gene\u2010knockout mice compared with controls. Upregulation of RAS components was positively associated with increased plasma levels of lipid profile. The <jats:italic>in vitro<\/jats:italic> study further confirmed that cholesterol loading increased supernatant renin activity and Ang II level of HepG2 cells, accompanied by increased ECM production that was positively associated with increased expression of intracellular RAS components. Interestingly, Ang II treatment increased lipid accumulation in livers of C57BL\/6 mice and HepG2 cells. Furthermore, Ang II treatment increased gene and protein expression of sterol regulatory element\u2013binding protein (SREBP) cleavage activating protein (SCAP), SREBP\u20102 and LDLr, which were mediated by enhanced SCAP\/SREBP\u20102 complex translocation from endoplasmic reticulum to Golgi. However, LDLr pathway was accordingly downregulated in livers of AT1 gene\u2010knockout C57BL\/6 mice or in HepG2 cells treated by telmisartan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings demonstrate that lipid disorder and intrahepatic RAS activation synergistically accelerate NAFLD progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13131","type":"journal-article","created":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T00:11:32Z","timestamp":1459383092000},"page":"1525-1534","source":"Crossref","is-referenced-by-count":42,"title":["Lipid disorder and intrahepatic renin\u2013angiotensin system activation synergistically contribute to non\u2010alcoholic fatty liver disease"],"prefix":"10.1111","volume":"36","author":[{"given":"Yu","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital Southeast University School of Medicine Nanjing City Jiangsu Province 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