标题：GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway
作者：He, Qin; Sha, Sha; Sun, Lei; Zhang, Jing; Dong, Ming
作者机构：[He, Qin; Sha, Sha; Sun, Lei; Zhang, Jing; Dong, Ming] Shandong Univ, Qilu Hosp, Dept Endocrine & Metab, 107 Wenhua Xi Rd, Jinan 250012, Peoples R Chi 更多
通讯作者地址：[Dong, M]Shandong Univ, Qilu Hosp, Dept Endocrine & Metab, 107 Wenhua Xi Rd, Jinan 250012, Peoples R China.
来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
关键词：Liraglutide; Hepatocyte steatosis; Autophagy; mTOR; AMPK
摘要：The incidence of nonalcoholic fatty liver disease (NAFLD) keeps rising year by year, and NAFLD is rapidly becoming the most common liver disease worldwide. Clinical studies have found that glucagon-like peptide-1 (GLP-1) analogue, liraglutide (LRG), cannot only reduce glucose levels, but also improve hepatic lipase, especially in patients also with type 2 diabetes mellitus (T2DM). In addition, enhancing autophagy decreases lipid accumulation in hepatocytes. The aim of the present study is to explore the effect of LRG on hepatocyte steatosis and the possible role of autophagy. We set up an obesity mouse model with a high-fat diet (HFD) and induced hepatocyte steatosis with free fatty acids (FFA) in human L-O2 cells. LRG and two inhibitors of autophagy, Chloroquine (CQ) and bafilomycin A1 (Baf), were added into each group, respectively. The lipid profiles and morphological modifications of each group were tested. Immunohistochemistry, immunofluorescence staining and transmission electron microscopy (TEM) were used to measure autophagy in this study. The autophagy protein expression of SQSTM1 (P62), and LC3B, along with the signaling pathway proteins of mTOR, phosphorylated mTOR (p-mTOR), AMPK, phosphorylated AMPK (p-AMPK) and Beclin1, were evaluated by western blot. Our results showed that LRG improved hepatocyte steatosis by inducing autophagy, and the AMPK/mTOR pathway is involved. These findings suggest an important mechanism for the positive effects of LRG on hepatic steatosis, and provide new evidence for clinical use of LRG in NAFLD. (C) 2016 Elsevier Inc. All rights reserved.