Mechanism of GLP-1 Receptor Agonists-Mediated Attenuation of Palmitic Acid-Induced Lipotoxicity in L6 Myoblasts

Abstract

Object. L6 cells were cultured to explore the possible mechanism underlying the improvement of insulin resistance by Liraglutide (LR). Methods. Cells were divided into 5 groups—control, high-fat, 10 nmol/L $\text{LR}+0.6$  mmol/L palmitic acid (PA) (10LR), 100 nmol/L $\text{LR}+0.6$  mmol/L PA (100LR), and 1000 nmol/L $\text{LR}+0.6$  mmol/L PA (1000LR). CCK-8 method to detect cell viability, GPO-PAP enzymatic method to detect intracellular triglyceride content, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting methods to detect fatty acid translocase CD36 (FAT/CD36) and fatty acid binding protein 4 (FABP4) in L6 cells, glucose-regulated protein 78 (GRP78), glucose transporter 4 (GLUT4) expression at the mRNA and protein levels, respectively, were performed. Results. We found that after PA intervention for 24 h, the cell viability decreased significantly; the cell viability of the LR group was higher than that of the high-fat group ( $P<0.01$ ). After PA intervention, compared with those in the high-fat group, GRP-78, FAT/CD36, FABP4 mRNA ((4.36 ± 0.32 vs. $8.15\pm 0.35$ ); ( $1.00\pm 0.04$ vs. $2.46\pm 0.08$ ); ( $2.88\pm 0.55$ vs. $8.29\pm 0.52$ ), $P<0.01$ ) and protein (( $3338.13\pm 333.15$ vs. $4963.98\pm 277.29$ ); ( $1978.85\pm 124.24$ vs. $2676.07\pm 100.64$ ); ( $3372.00\pm 219.84$ vs. $6083.20\pm 284.70$ ), both $P<0.01$ ) expression decreased in the LR group. The expression levels of GLUT4 mRNA (( $0.75\pm 0.04$ vs. $0.34\pm 0.03$ ), $P<0.01$ ) and protein (( $3443.71\pm 191.89$ vs. $2137.79\pm 118.75$ ), $P<0.01$ ) increased. Conclusion. Therefore, we conclude that LR can reverse PA-induced cell inactivation and lipid deposition, which may be related to the change in GRP-78, FAT/CD36, FABP4, GLUT4, and other factors.