Effects Of Betatrophin On Glucose And Lipid Metabolism In Db/db Mice

ObjectiveBetatrophin is a newly discoveredsecretory protein mainly expressed in liver and adipose tissue.Recent studies have found that it may be associated with glucose and lipid metabolism.In this study,the effect of Betatrophin on blood lipid and blood glucose in db/db mouse was observed for the first time,while the effects on the expression of genes related to glucose and lipid metabolism were also analyzed effectively.MethodsThis study selected type 2 diabetic mouse as animal model.In the experiment,healthy 8-week-old SPF mice were randomly divided into two groups: experimental group and control group.The empty vector adenoviruses and over-expressed Betatrophin adenovirus were injected into db/db mice by hydrodynamic injection of caudal vein for 8 consecutive days.On the 8th day,the effect of triglyceride,cholesterol and low density lipoprotein on lipid metabolism was evaluated by measuring serum triglyceride,cholesterol and low density lipoprotein.On day 4 and day 6,the effect of glucose tolerance test and insulin stimulation test on blood glucose and insulin sensitivity were observed respectively.The effects of PEPCK,G6 Pase,ATGLand ANGPTL3 on the expression of glycolipid metabolism-related genes were observed by using Realtime PCR.Results(1)In this study,the primary liver cells were infected with amplified over-expressed Betatrophin adenovirus and empty vector adenoviruses.The results showed that the mRNA level of Betatrophin in the experimental group was 12.6 times higher than that in the control group.Compared with the control group,the protein level of the experimental group also increased significantly.(2)Two viruses were injected into db/db mice.Compared with the control group,The mRNA level of Betatrophin in the experimental group rose significantly in liver tissue.The difference is statistically significan(P<0.05).In the course of eight-day experiment,there were no significant changes in body weight,food intake,liver weight and fat weight in the two groups of db/db mice.(3)In terms of lipid metabolism effects,serum triglyceride levels in the experimental group were significantly higher than those in the control group(4.31±1.24 vs.1.67±0.50 mmol/L,P<0.001).The level of HDL in experimental group was significantly lower than that in control group(1.59±0.27 vs.2.40±0.42 mmol/L,P<0.01).The difference was statistically significant.There was no significant difference in the levels of total cholesterol,low density lipoprotein,albumin and globulin between the two groups.In terms of factors related to Lipid Metabolism,the expression level of ATGL gene in the experimental group was significantly reduced compared with the control group(P<0.05).The difference is statistically significant.(4)In terms of glucose metabolism,the results of glucose tolerance test showed that no significant differences in glucose levels were found among the 5 time points,such as 0 minutes,30 minutes,60 minutes,90 minutes,120 minutes and so on compared with the control group.The results of insulin excitatory test showed that glucose levels decreased significantly at all five time points in the experimental group.Compared with the control group,the difference is statistically significant.In terms of factors related to glucose metabolism,The expression level of PEPCK gene in experimental group mice was significantly decreased compared with the control group(P<0.05).The difference is statistically significant.(5)In terms of effects on liver function,the serum alkaline phosphatase level in the experimental group was significantly increased compared with the control group(P<0.001).The difference is statistically significant.There was no difference in direct bilirubin and total bile acid levels between the two groups.In relation to the effect of the relevant factors on the secretion of the liver,the level of ANGPTL3 gene in experimental group decreased significantly(P<0.01).The difference is statistically significant.The expression levels of FGF21 and SHBG were not significantly changed ConclusionOverexpression of Betatrophin in db/db mouse leads to the elevation of serum triglyceride level and decrease of ATGL gene expression level.Betatrophin may be involved in lipid metabolism through the regulation of ATGL gene level.But its effect on glucose metabolism needs further study.But its effect on glucose metabolism needs further study.