Metformin might alleviate hepatic lipid accumulation in high-fat-diet-induced mice via adenosine monophosphate-activated protein kinase signaling pathway

Objective To observe the effects of metformin on hepatic lipid accumulation in high-fat-diet-induced C57BL/6J mice and discuss its mechanism. Methods Non-alcoholic fatty liver disease (NAFLD) models were established by feeding C57BL/6J mice with a high-fat-diet for 6 weeks. C57BL/6J mice aged 10 weeks were divided into three groups as followings: normal diet group (ND group, n=10, fed with a normal chow diet), high-fat diet group (HFD group, n=12, fed with a high fat diet and given 300 μl of saline by gastric perfusion once a day) and metformin group (Met group, n=12, fed with a high-fat diet and given 300 μl of saline dissolving with 300 mg/kg of metformin by gastric perfusion once a day). Body weight, the amount of food intake, serum lipids, hepatic enzymes, hepatic lipid infiltration, contents of hepatic triglyceride (TG), total cholesterol (TC) and expression levels of proteins related to lipid metabolism in liver tissue were compared among those 3 groups after 4-week intervention. The t test was performed in data comparisons between two groups, while one-way analysis of variance was applied for comparisons among multiple groups. Results Compared with HFD group, body weight of mice in Met group decreased significantly [(32.9±1.1) vs (36.4±1.1) g, t=2.257, P 0.05). Compared with HFD group, the concentrations of TG, low-density lipoprotein-cholesterol, alanine transaminase and aspartate aminotransferase were prominently decreased by metformin intervention (t=2.285-2.860, all P<0.05). Compared with HFD group, the hepatic lipid infiltration was notably alleviated in Met group (t=28.000, P<0.001). Moreover, the contents of TG and TC in liver tissue were remarkably decreased in Met group (t=2.394, 2.281, both P<0.05). Compared with HFD group, phosphorylation of adenosine monophosphate-activated protein kinase α (AMPKα) and acetyl coenzyme A carboxylase were significantly enhanced whereas protein expressions of sterol regulatory element binding transcription factor 1-c and fatty acid synthase were notably decreased after 4-week metformin intervention (0.82±0.07 vs 0.59±0.03, 0.94±0.12 vs 0.42±0.10, 1.24±0.05 vs 1.56±0.08, 1.09±0.07 vs 1.42±0.06, t=-2.892, -3.463, 3.447, 3.507, all P<0.05). Conclusion Metformin might alleviate hepatic lipid accumulation in high-fat-diet-induced C57BL/6J mice via AMPK signaling pathway, it suggests that metformin can be a promising treatment for NAFLD. Key words: Metformin; Non-alcoholic fatty liver disease; Hepatic lipid accumulation; Adenosine monophosphate-activated protein kinase