Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT/mTOR/SREBP-1 signaling pathway

作     者：Jie Hu Wei Hong Kan-Nan Yao Xiao-Hong Zhu Zhi-Yun Chen Lei Ye 

作者机构：Department of Infectious Diseases The First Affiliated Hospital of Zhejiang Chinese Medical University the Second Central Laboratory The First Affiliated Hospital of Zhejiang Chinese Medical University 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2019年第25卷第12期

页      面：1492-1501页

核心收录：

学科分类：10[医学] 

基　　金：Supported by the Natural Science Foundation of Zhejiang Province China No.LQ19H290001 

主　　题：Ursodeoxycholic acid Hepatic lipid metabolism AKT/mTOR/SREBP-1 Hepatic steatosis 

摘      要：BACKGROUND Nonalcoholic fatty liver disease(NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis(NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeoxycholic acid(UDCA)play an essential role in the pathogenesis of NAFLD by regulating the level of sterol regulatory element-binding protein(SREBP) 1 c, but the underlying regulatory mechanism remains elusive. Increased evidence indicates that the AKT/mTOR/SREBP-1 signaling pathway is a key pathway to regulate hepatic cellular lipid metabolism. UDCA may regulate the AKT/mTOR/SREBP-1 signaling pathway to ameliorate hepatic lipid *** To investigate the functional mechanism of UDCA in an oleic acid(OA)-induced cellular model of *** The cellular model of NAFLD was established using OA and treated with ***, the best concentration of UDCA was selected. For the best time-dependent assay, cells were stimulated with OA only or co-treated with OA and 2 mmol/L UDCA for 24 h, 48 h, and 72 h. Oil red O staining was used to observe the accumulation of intracellular lipids, while the intracellular contents of triglyceride, alanine aminotransferase(ALT), gamma-glutamyl transpeptidase(GGT), and aspartate aminotransferase(AST) were detected by enzymatic methods. Meanwhile, the expression levels of AKT/mTOR/SREBP-1 signaling pathway-related proteins were detected by real-time PCR and Western *** In the NAFLD cell model established with LO2 cells induced using OA, lipid accumulation was obvious. UDCA significantly inhibited lipid accumulation at different concentrations(especially 2 mmol/L) and decreased cell growth ability at different time points. The biochemical parameters like ALT, AST, and GGT were significant improved by UDCA. UDCA treatment vividly repressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in LO2 cells induced with *** Our findings demonstrate the effect of UDCA in improving NAFLD. U