title: GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway.
abstract: 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.
authors.affiliation: Department of Endocrine and Metabolism, Qilu Hospital of Shandong University, Shandong University, 107#Wenhua Xi Road, Jinan, 250012, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Endocrine and Metabolism, Qilu Hospital of Shandong University, Shandong University, 107#Wenhua Xi Road, Jinan, 250012, PR China.
authors.forename: Sha
authors.initials: S
authors.lastname: Sha
authors.affiliation: Department of Endocrine and Metabolism, Qilu Hospital of Shandong University, Shandong University, 107#Wenhua Xi Road, Jinan, 250012, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Endocrine and Metabolism, Qilu Hospital of Shandong University, Shandong University, 107#Wenhua Xi Road, Jinan, 250012, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Endocrine and Metabolism, Qilu Hospital of Shandong University, Shandong University, 107#Wenhua Xi Road, Jinan, 250012, PR China. Electronic address: dr_dongming@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D000069450:Liraglutide / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D008055:Lipids; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMPK; Autophagy; Hepatocyte steatosis; Liraglutide; mTOR