| Objective:In this experiment,high-fat-induced obese mice were used as the research objects,and liraglutide was applied to intervene,and the mice administeredwith liraglutide were compared with mice not administered with liraglutide.The body weight and fat weight of each group of mice were measured,and the levels of glucolipidmetabolism indexes and related inflammatory factors were detected,and the expression levels of SIRT1,PGC-la,PEPCK genes and proteins were detected in each group of mice.By establishing animal model experiments,to evaluate the regulation of overall glucolipid metabolism and the improvement of body weight in high-fat induced obese mice by applying liraglutide.Further study the effect of liraglutide on hepatic lipid metabolism in high-fat induced obese mice.To further investigate the mechanism of action of liraglutide in improving hepatic lipid metabolism.Methods:Eighteen mice（healthy C57BL/6 mice,7-8 weeks old,male,purchased from the Institute of Comparative Medicine,Yangzhou University）were randomly divided into normal control group（NC group）,model control group（OC group）and liraglutide group,with 6 mice in each group（n=6 in NC group,n=6 in OC group and n=6 in liraglutide group）.After all mice were acclimatized for 1 week,the mice in the normal control group continued to be fed with standard chow,while the mice in the model control group and the mice in the liraglutide group were fed with high-fat chow for 12 weeks to establish the obese mouse model.After weighing the mice in the liraglutide group,the amount of liraglutide was calculated at 400μg/（kg*day）for each mouse and administered intraperitoneally for one week.Mice in the normal control group and mice in the model control group were injected intraperitoneally with equal volumes of saline.After the experiment,the body weight of mice was measured;fasting blood glucose,glucose tolerance and insulin tolerance were measured by rapid glucometer;serum insulin,IL-6 and TNF-a levels were measured by ELISA;the expression of mouse liver peroxisome proliferator-activated receptor y coactivator la（PGC-la）and its related pathway proteins were measured by Western blotting.The mRNA expression levels of PGC-1a and its related pathways in mouse liver were measured by Real-Time PCR.The measurement data were expressed as mean ± standard deviation（x ± S）,and one-way ANOVA was used for comparison between groups,and P<0.05 was considered statistically significant.Results:（1）The body weight and fat weight of mice in the model control group were elevated compared with those in the normal control group（P<0.05）.The body weight and fat weight of mice in the liraglutide group were significantly reduced compared with those in the model control group（P<0.05）.（2）Compared with normal control mice,fasting glucose and fasting insulin were elevated（P<0.05）,glucose tolerance and insulin tolerance were decreased（P<0.05）,and area under the glucose tolerance curve and area under the insulin tolerance curve were significantly increased（P<0.05）in the model control mice.Compared with the model control group,the mice in the liraglutide group had lower fasting glucose and fasting insulin（P<0.05）,improved glucose tolerance and insulin tolerance（P<0.05）,and significantly decreased area under the glucose tolerance curve and area under the insulin tolerance curve（P<0.05）.（3）Serum triglyceride（TG）levels,serum cholesterol（TC）levels,hepatic TG,hepatic TC and liver weight were increased in model control mice compared with normal control mice（P<0.05）.Compared with the model control group,mice in the liraglutide group had significantly lower serum triglycerides and total cholesterol（P<0.05）,and significantly lower liver TG,liver TC and liver weight（P<0.05）.（4）Serum IL-6 levels and TNF-a levels were significantly increased in model control mice compared with normal control mice（P<0.05）.Compared with the model control group,the serum inflammatory factors IL-6 and TNF-a were significantly lower in the mice in the liraglutide group（P<0.05）.（5）The gene and protein levels of hepatic SIRT-1,PGC1a,and PEPCK were significantly lower in the model control group mice compared with the normal control group mice（P<0.05）.Compared with the model control group,the gene and protein levels of liver SIRT-1,PGC-1a and PEPCK were significantly increased in the liraglutide group（P<0.05）.Conclusion:High-fat diet can induce abnormal glucolipid metabolism and cause hepatic steatosis in mice.Liraglutide was able to improve glucolipid metabolism,enhance hepatic fatty acid oxidation and reduce hepatic fat accumulation in high-fat diet-induced obese mice,and the mechanism may be related to activation of hepatic SIRT1/PGC-la/PEPCK pathway. |
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