Mechanism of metformin decreasing the cholesterol and triglyceride contents in the liver of high-fat diet fed rats / 中华内分泌代谢杂志

ABSTRACT

Objective To detect the expression and activity of AMP-activated protein kinase α subunit (AMPKα) and peroxisome proliferator-activated receptor-α (PPARα) in liver of high-fat fed rats treated with metformin, and to investigate the mechanisms underlying metformin decreasing the total cholesterol (TC) and triglyceride (TG) contents of the liver. Methods Total 30 male Wistar rats were randomly divided into control group (group C), high-fat diet fed group (group HF) and high-fat diet feeding plus metformin treatment group (group Met,metformin was administered orally at the last month of high-fat diet feeding). After feeding for 5 months, TC and TG in liver and sera were determined, respectively. The mRNA and protein levels and activity of AMPKα and PPARα in the liver were determined by real-time PCR and Western blotting. The activity of PPARα transcriptor binding to DNA was detected by ELISA. Results Five months of high-fat diet feeding induced a significant decrease in AMPKα and phosphorylated-AMPKα protein expression as well as AMPKα2 and PPARα mRNA levels in the liver of rats (all P＜0.05), while it did not alter PPARα protein expresssion and the PPARα activity binding to DNA as well as AMPKα1 mRNA levels. The TC and TG contents in the liver (P＜0.05) and serum (P＜0.05) were sharply increased in group HF than those in group C. Treatment with metformin for 1 month led to a marked increase of AMPKα2 mRNA level, AMPKα and phosphorylated-AMPKα protein expression as well as the PPARα activity in group Met compared with group HF(all P＜0.05), while the PPARα protein expression and the PPARα mRNA level did not show significant change. Consistent with these findings, the TC and TG contents in rat liver as well as sera were strikingly decreased (all P＜0.05). Conclusion The activations of AMPKα and PPARα induced by metformin may contribute to the decrease of TC and TG content in liver and sera of the high-fat fed rats.