Effect Of Telmisartan On Visceral Adipose Tissue In Long-Term High-Fat-Fed Mice

Objective:1.To observe the effect of telmisartan on body weight,insulin resistance and fasting plasma glucose(FPG) of SD rats with a long-term high sugar and fat diet(HSHFD).2.To observe the effect of telmisartan on the adipocyte size in epididymal fat tissue,the adipose tissue macrophage quantity and polarization in SD rats with a HSHFD and to discuss the possible machanism of effect on degree of insulin resistance induced by telmisartan.Methods:The clean littermate male SD rats aged from 6 to 8 weeks were randomly divided into a control group(8) and a model group(24).The rats were fed a standard diet for 36 weeks in the control group,the rats were fed a HSHFD for 24 weeks in the model group,then the rats were randomly divided into three groups: the HSHF group(HSHF,n=8),the HSHF+Tel group(Tel,n = 8) and the HSHF+Saline group(Sal,n=8).The rats were fed as before for 12 weeks in the HSHF group;the rats were fed a HSHFD and telmisartan(5mg/kg/d,dissloved in 2 ml saline with a intragastric administration) for 12 weeks in the Tel group;the rats were fed a HSHFD and 2 ml saline with a intragastric administration for 12 weeks in the Sal group.At the end of the experiment(36 weeks), 6 rats were randomly selected were examined from each group.Experimental methods:1.The rats were fasted for 12 hours,weighed and were anesthetized using urethane,the blood were collected from the abdominal aorta and managed with conventional centrifuge under 3000r/min for 15 minutes,we tested thefollowing indicators in the same batch:fasting blood glucose(FPG),fasting serum insulin(FINS)and serum triglyceride(TG).Insulin resistance index was calculated(HOMA-IR,HOMA-IR = FINS×FBG /22.5).2.The left epididymal adipose tissues were collected and immediately fixed in 10% neutral buffered formalin, embedded in paraffin and routinely stained using hematoxylin and eosin,the adipocyte size were observe with optical microscope.The expression of macrophage marker CD68 in adipose tissues were examined by immunohistochemistry;the right epididymal adipose tissues were immediately collected,throwed into liquid nitrogen and then moved to-80℃ fridge.The gene expressions of M1 and M2 markers including i NOS and Arg1 in adipose tissues were then examined by RT-PCR.Results:1.The change of body weight of rats in each groupCompared with the control group,BW in the HSHF group was significantly higher,the differences were statistically significant(P <0.05);Compared with the HSHF group,BW in the Tel group was significantly lower,the differences were statistically significant(P <0.05);The differences of BW between the HSHF group and the Sal group were not statistically significant( P>0. 05).2.The change of FPG、TG、FINS and HOMA-IR of rats in each groupCompared with the control group,FPG、TG、FINS and HOMA-IR in the HSHF group was significantly higher,the differences were statistically significant(P<0.05);Compared with the HSHF group,FPG、TG、FINS and HOMA-IR in the Tel group was significantly lower,the differences were statistically significant(P<0.05);The differences of FPG、TG、FINS and HOMA-IR between the HSHF group and the Sal group were not statistically significant( P>0. 05).3.The change of the epididymal adipocyte size of rats in each groupThe adipocyte size is almost same and small in control group. On thecontrary,the adipocyte size is quite different and large in HSHF group,which is similar to that of the Sal group. Compared with HSHF group,the adipocyte size is decreased in Tel group.4.The change of expression of macrophage marker CD68 in epididymal adipose tissues of rats in each groupCompared with the control group, the expression of macrophage marker CD68 in the HSHF group was significantly higher,the differences were statistically significant(P <0.05);Compared with the HSHF group,expression of CD68 in the Tel group was significantly lower,the differences were statistically significant(P<0.05);The differences of expression of CD68 between the HSHF group and the Sal group were not statistically significant( P>0. 05).5.The change of expression of M1 macrophage marker i NOS in epididymal adipose tissues of rats in each groupCompared with the control group, the expression of M1 macrophage marker i NOS in the HSHF group was significantly higher,the differences were statistically significant(P <0.05);Compared with the HSHF group,expression of i NOS in the Tel group was significantly lower,the differences were statistically significant(P<0.05);The differences of expression of i NOS between the HSHF group and the Sal group were not statistically significant( P>0. 05).6.The change of expression of M2 macrophage marker Arg1 in epididymal adipose tissues of rats in each groupCompared with the control group, the expression of M2 macrophage marker Arg1 in the HSHF group was significantly lower,the differences were statistically significant(P <0.05);Compared with the HSHF group,expression of Arg1 in the Tel group was significantly higher,the differences were statistically significant(P <0.05);The differences of expression of Arg1 between the HSHF group and the Salgroup were not statistically significant( P>0. 05).Conclusion:1.Telmisartan can prevent body weight gain and improve glucose and lipid metabolish and insulin resistance in rats fed with a long-term HSHFD.2.Telmisartan can reduce the adipocyte size and fat content in epididymal fat tissue of rats fed with a long-term HSHFD.Moreover,telmisartan can reduce the number of macrophage and switch the macrophage polarization from M1 to M2,therefore alleviate the inflammation in adipose tissue, possibly resultting in the improvement on insulin resistance.