Abstract: Objective: To investigate the effects of liraglutide combined with vitamin D on high-fat-induced non-alcoholic fatty liver disease (NAFLD) mice and its potential mechanism. Methods: C57BL/6 mice were divided into control group, NAFLD model group, liraglutide group, vitamin D group and liraglutide combined with vitamin D group. Each group consisted of 10 mice. The control group was fed with normal diet for 12 weeks; the model group was fed with high-fat diet for 12 weeks; the liraglutide group, vitamin D group and combined group were fed with high-fat diet for 12 weeks, From the 9th week, the three groups of mice were intraperitoneally injected with liraglutide (0.6 mg/kg), vitamin D(250 mg/(kg·d) ) by gavage, and combination. After 12 weeks of feeding, the blood and liver tissues of mice in each group were collected for biochemical and pathological examination, and the phosphorylation level of AMP-activated protein kinase (AMPK) in liver tissues of mice in each group was detected by immunoblotting. Results: Liraglutide or vitamin D alone or in combination could improve liver lipid accumulation (triglycerides: 6.0±0.7 vs 3.8±0.3, 3.9±0.3 and 2.1±0.2, all P＜0.05; cholesterol: 1.4±0.5 vs 0.9±0.2, 0.8±0.2 and 0.5±0.1, all P＜0.05) and steatosis (NAFLD activity score: 2.4±0.3 vs 1.0±0.2, 0.9±0.1 and 0.6±0.1, all P＜0.05) in NAFLD mice. In addition, compared with liraglutide or vitamin D group, liraglutide combined with vitamin D treatment was more effective, and might be related to the regulation of insulin resistance and AMPK phosphorylation. Conclusion: The results showed that vitamin D could enhance the therapeutic effect of liraglutide on NAFLD induced by high fat, and may be related to the regulation of insulin resistance and AMPK phosphorylation.

Key words: liraglutide, vitamin D, nonalcoholic fatty liver, mice