Liraglutide reduces lipid accumulation in steatotic L-02 cells by enhancing autophagy

• Published in: Molecular medicine reports Vol. 10; no. 5; pp. 2351 - 2357
• Main Authors: ZHOU, SHI-WEI, ZHANG, MAN, ZHU, MIN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.11.2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Analysis; Apoptosis; Autophagy; Autophagy (Cytology); Autophagy - drug effects; Benign; Cell Line; Cytotoxicity; Diabetes; Drug Evaluation, Preclinical; Drug therapy; Electron microscopy; Experiments; Fatty acids; Fatty Acids, Nonesterified - metabolism; Fatty liver; Fatty Liver - drug therapy; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - pharmacology; Health aspects; hepatic steatosis; Hepatocytes; Humans; Kinases; Lipid Metabolism - drug effects; Lipids; Liraglutide; Liver - pathology; Liver diseases; Metabolism; Microtubule-associated protein 1; mRNA; non-alcoholic fatty liver disease; Oleic acid; Oxidative Stress; Palmitic acid; Phagocytosis; Rapamycin; Rodents; Steatosis; Studies; Weight control; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2014.2569

Simple hepatic steatosis is the early stage of non-alcoholic fatty liver disease and is recognized as a benign process. Previous studies show that glucagon-like peptide-1 has great potential in improving hepatic steatosis. Recent data have revealed that inhibiting autophagy exacerbates lipid accumulation in hepatocytes. Therefore, the present study aimed to determine the effects of liraglutide (LG) on simple hepatic steatosis and the possible role of autophagy. Firstly, steatotic L-02 cells were induced by incubating L-02 cells with 1 mmol/l free fatty acid (FFA) mixture (oleic acid and palmitic acid at a molar ratio of 2:1) for 24 h. Intracellular lipid accumulation, cell viability, oxidative stress and apoptosis were evaluated. Secondly, steatotic L-02 cells were treated with 10 or 100 nmol/l LG, 100 nmol/l LG plus 3-methyladenine (3-MA), or rapamycin for 24 h, and then lipid accumulation was measured. Next, the degree of lipid accumulation and the intensity of autophagy were assessed. Oil red O staining and triglyceride quantification demonstrated notable steatosis in L-02 cells following exposure to 1 mmol/l FFA mixture for 24 h. There was no significant cytotoxicity, oxidative stress or apoptosis in steatotic L-02 cells. Treatment with 100 nmol/l LG reduced lipid accumulation in steatotic L-02 cells and increased the mRNA levels of microtubule-associated protein 1 light chain 3B. Additionally, it enhanced the autophagic flux in steatotic L-02 cells, as measured by western blot analysis and shown by electron microscopy. Additionally, 3-MA weakened the ability of LG to improve hepatic steatosis and enhance autophagy. Our data indicate that LG reduces the lipid accumulation in steatotic L-02 cells, and the activation of autophagy plays a significant role in this process.