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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 themore » 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. -- Highlights: •Liraglutide reduces lipid accumulation in hepatic steatosis both in vivo and in vitro. •Autophagy was involved in relieving effects of liraglutide on hepatic steatosis. •AMPK/mTOR pathway was involved in liraglutide-induced autophagy.« less

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
22598786
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 476; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARBOXYLIC ACIDS; DIABETES MELLITUS; DIET; FATS; GLUCAGON; GLUCOSE; IN VITRO; IN VIVO; LIPASES; LIPIDS; LIVER; LIVER CELLS; MICE; PATIENTS; TRANSMISSION ELECTRON MICROSCOPY

Citation Formats

He, Qin, Sha, Sha, Sun, Lei, Zhang, Jing, and Dong, Ming, E-mail: dr_dongming@126.com. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.05.086.
He, Qin, Sha, Sha, Sun, Lei, Zhang, Jing, & Dong, Ming, E-mail: dr_dongming@126.com. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway. United States. doi:10.1016/J.BBRC.2016.05.086.
He, Qin, Sha, Sha, Sun, Lei, Zhang, Jing, and Dong, Ming, E-mail: dr_dongming@126.com. Fri . "GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway". United States. doi:10.1016/J.BBRC.2016.05.086.
@article{osti_22598786,
title = {GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway},
author = {He, Qin and Sha, Sha and Sun, Lei and Zhang, Jing and Dong, Ming, E-mail: dr_dongming@126.com},
abstractNote = {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. -- Highlights: •Liraglutide reduces lipid accumulation in hepatic steatosis both in vivo and in vitro. •Autophagy was involved in relieving effects of liraglutide on hepatic steatosis. •AMPK/mTOR pathway was involved in liraglutide-induced autophagy.},
doi = {10.1016/J.BBRC.2016.05.086},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 476,
place = {United States},
year = {Fri Aug 05 00:00:00 EDT 2016},
month = {Fri Aug 05 00:00:00 EDT 2016}
}