Metformin promotes autophagy in muscle cells exposed to palmitic acid through AMPK/SIRT3 pathway / 中华内分泌代谢杂志

ABSTRACT

Objective@#To investigate the effect of metformin on autophagy in muscle cells exposed to palmitic acid, and to explore its mechanism.@*Methods@#L6 rat myoblasts were incubated with palmitic acid at various concentrations(0.1, 0.2, 0.4, 0.6 mmol/L) and metformin(0.5, 1, 2, 5, 10 mmol/L) for 24 h. CCK8 method was used to detect the survival rate of muscle cells. After muscle cells were treated with palmitic acid and metformin for 24 h, mRNA and protein expressions of microtubule-associated protein11ight chain3(LC3Ⅱ), Beclin 1, p62, and silent mating type information regulation2 homolog-3(SIRT3) were detected by RT-PCR and Western blot, respectively. AMP-activated protein kinase(AMPK) phosphorylation level was detected by Western blot.@*Results@#Palmitic acid dose-dependently decreased the survival rate of muscle cells, which was attenuated by metformin at the concentration of 2 mmol/L. After muscle cells were incubated with 0.4 mmol/L palmitic acid and 2 mmol/L metformin for 24 h, palmitic acid significantly reduced the mRNA and protein expressions of LC3Ⅱ, Beclin1, and SIRT3 as well as phosphorylation level of AMPK(all P<0.05), and increased p62 mRNA and protein expressions(P<0.05). Those effects were all antagonized by metformin(all P<0.05).@*Conclusions@#Metformin treatment may promote the autophagy of muscle cells exposed to palmitic acid through AMPK/STRT3 pathway.