Combination of metformin and chlorogenic acid attenuates hepatic steatosis and inflammation in high-fat diet fed mice

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become an important health problem in the world. Natural products, with anti-inflammatory properties, are potential candidates for alleviating NAFLD. Metformin (MET) and chlorogenic acid (CGA) have been reported to be effective in the improvement of NAFLD. Here, we aimed to evaluate the efficacy of MET and CGA combination in ameliorating NAFLD in high-fat diet (HFD) fed mice. Fifty C57BL/6 male mice were divided into two groups, one fed a standard chow diet (n = 10) and the other was fed an HFD (n = 40) for 10 weeks. Animals in the HFD group were then randomly divided into a four groups (HFD, HFD + MET (0.25%), HFD + CGA (0.02%) and HFD + MET + CGA (0.25 + 0.02%). MET and CGA combination decreases fasting blood glucose and improves glucose intolerance. Decreased hepatic triglyceride level was associated with lower expression levels of fatty acid synthase and sterol regulatory element-binding protein-1c in MET+CGA treated mice. MET and CGA combination treatment resulted in the polarization of macrophages to the M2 phenotype, reduction of the expression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), and decreasing protein level of NF-kB p65. It was found that the lowering effect of combined MET and CGA on the expression of gluconeogenic genes was accompanied by increasing phosphorylation of glycogen synthase kinase 3β. Treatment of HFD mice with the combination of MET and CGA was found to be more effective at alleviating inflammation and lipid accumulation by increasing phosphorylation of AMP-activated protein kinase. In conclusion, these findings suggest that the MET + CGA combination might exert therapeutic effects against NAFLD.