Effect and mechanism of liraglutide on the apoptosis of human hepatocellular carcinoma HepG2 cells induced with palmitic acid

Objective To observe whether liraglutide protects HepG2 cells from lipotoxicity by affecting mitogen-activated protein kinase (MAPKs) pathway. Methods HepG2 cells were induced with 400μmol/L palmitic acid, and cells were treated with a final concentration of 100 nmol/L liraglutide. In addition, JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) were added in advance, respectively. Apoptosis rate, malondialdehyde (MDA) content, and caspase3 activity were detected. Western blot was used to detect p38 mitogen-activated protein kinase (p38 MAPK), c-jun amino terminal kinase (JNK), cytochrome oxidase P450 2E1 (CYP2E1), glucose regulatory protein 78 (GRP78), activated caspase 3, B cell lymphoma associated Protein X (Bax), B cell lymphoma 2 (Bcl-2), and expression of C/EBP homologous protein (CHOP) protein. LSD or Dunnett’s T3 test were used to compare the mean of multiple samples. Results Palmitic acid increased the phosphorylation of p38 MAPK and JNK in HepG2 cells (P 0.05) after pretreatment with those two inhibitors. Conclusion Palmitic acid has strong lipotoxicity to HepG2 cells and induces apoptosis. Glucagon-like peptide-1 analogue, liraglutide may improve lipotoxicity of palmitic acid by mediating p38 MAPK and JNK pathways. Key words: Apoptosis; Liraglutide; Endoplasmic reticulum stress; Oxidative stress