Paeonol prevents lipid metabolism dysfunction in palmitic acid-induced HepG2 injury through promoting SIRT1-FoxO1-ATG14-dependent autophagy.
This study aimed to investigate the effects of paeonol (Pae) on lipid metabolism in palmitic acid (PA)-induced injury of HepG2, and to evaluate the protective mechanisms. Lipid metabolism dysfunction of HepG2 cells was produced by administration of palmitic acid (PA). The cells were pretreated with different concentrations of Pae. MTT method was used to detect the cell survival; lipid metabolism was evaluated based on total cholesterol (TC), triglycerides (TG); Western blotting was used to detect the expression of Sirtuin 1 (SIRT1), autophagy related 14 (ATG14), microtubule-associated protein 1A/1B-light chain 3 (LC3) and p62 proteins; immunoprecipitation was used to detect the expression of acetylated FoxO1. After treatment for 24 h, the inhibitory concentration 50 (IC50) of PA in HepG2 cells was about 566.8 μM. Pae at the concentration range from 7.5 to 30 μM did not affect cell viability. Thus, 500 μM PA was used to model metabolism dysfunction and Pae at the concentration range was selected to investigate the protective effect. Compared with the normal control group, the cell survival rate decreased, the number of lipid droplets, and TC and TG levels increased in the model group. Compared with model group, the cell survival rate of Pae (7.5, 15, 30 μM) group increased, the number of lipid droplets and content of TC and TG decreased, the ratio of LC3-II/I increased and p62 expression decreased with pretreatment of Pae. Additionally, Pae pretreatment promoted SIRT1 and ATG14 expression, but reduced acetylated FoxO1 levels in PA-treated cells. Most importantly, autophagy inhibitor, as well as SIRT1 inhibitor blocked the effects of Pae on PA-induced cell injury and metabolism dysfunction, respectively. Pae prevents lipid metabolism dysfunction in PA-induced HepG2 injury by promoting SIRT1-FoxO1-ATG14-dependent autophagy.
['Dong|Zhaomin|Z|', 'Xie|Xianmei|X|', 'Sun|Yin|Y|', 'Wu|Hongfei|H|', 'Dai|Min|M|']
D000098:Acetophenones D033942:Adaptor Proteins, Vesicular Transport D001343:Autophagy D000071183:Autophagy-Related Proteins D002470:Cell Survival D002784:Cholesterol D000071161:Forkhead Box Protein O1 D056945:Hep G2 Cells D006801:Humans D050356:Lipid Metabolism D019308:Palmitic Acid D056564:Sirtuin 1 D014280:Triglycerides
Lipid metabolism Autophagy Hyperlipidemia Paenol SIRT1-FoxO1-ATG14