Effects Of PPARγ Agonist On Adiponectin Receptor 1 Of Obese Mice’s Podocyte

Objective: Today,Obesity has become a kind of common disease in the world,and a variety of complications caused by obesity has become a research hotspot. In this study, we based on the action mechanism of PPARγ(peroxisome proliferator activated receptor γ) agonist and pathogenesis of ORG to evaluate the effects of PPARγ agonist on the expression levels of serum ADP(adiponectin) and Adipo R1( adiponectin receptor 1) and 24 h urine m ALB(microalbumin) in the kidneys of obese mice, in order to explore the PPARγ agonist’s effect of preventing ORG.Methods: In this study, we took six weeks’ old male ob/ob mice and male C57BL/6J mice as the experimental subjects. 24 ob/ob mice were divided into three groups: obesity group(M group) and small doses pioglitazone treatment group(T1 group) and large doses pioglitazone treatment group(T2 group), ob/ob mice were all fed with high lipid chow. 8 C57BL/6J mice were fed with normal chow as the control group(C group). The mice of T1 and T2 should be administered with pioglitazone everyday, the doses of T1 was 2.25 mg·kg-1·d-1 and T2 was 6.65mg·kg-1·d-1, the other mice were administered with water at the same time. We measured T1 and T2 mice’s body weight every week to adjust pioglitazone’s doses. Each mouse’s serum ADP and urine m ALB and blood glucose were measured before and after experiment. After 12 weeks’ feeding, all mice were sacrificed, took their kidneys for research. We using microscope by HE staining and immunohistochemistry methods to observe and measure each mouse’s kidneys’ weight, the morphological changes of kidneys, glomerular diameters, the level of expression of ZO-1, percentage of podocytes which is signed with WT1,the level of expression of Adipo R1. We used SPSS17.0 to process and compare experimental data of each group’s mice. A value of P < 0.05 was considered statistically significant.Results: 1.Body mass and blood sugar :The average body weight of ob / ob mice was significantly higher than that of C57 BL / 6J mice at 6 weeks old(P<0.01), what’s more, the average body weight of ob / ob mice was not only significantly higher than that of C57 BL /6 mice(P<0.01), but more than 50% of the latter(> 20%), which means the ob / ob mice met the standards of obesity.Each mouse’s blood glucose was less than 16.7mmol/L, which exclude diabetes. there was no significant difference among the M and T1, T2 groups(P>0.05). At the end of the experiment the weight of group M and T1, T2 mice is more obviously higher than that in group C(P<0.01),and group T2 was much higher than group T1(P<0.01). The weight of all group after experiment were higher than that before(P<0.01). 2. Serum concentrations of ADP:Before experiment, the mice’s serum ADP of T1,T2 and M group is lower than C group(P<0.01), the data of T1,T2,M group is similar(P>0.05). After experiment, the mice’s serum ADP of T1,T2 is higher than M group(P<0.01) and T2 is higher than T1(P<0.01). Compared before, there is little change in the mice’s serum ADP of C group(P>0.05). 3.24 h m ALB:Before experiment, the mice’s urine m ALB of T1,T2 and M group is higher than C group(P<0.01), the data of T1,T2,M group is similar(P>0.05). After experiment, the mice’s urine m ALB of T1,T2 is lower than M group and higher than C group(P<0.01), T2 is lower than T1(P<0.01). Compared before, there is little change in the mice’s urine m ALB of C group(P>0.05). 4.Pathological changes of kidney : The C group’s mice’s glomerular is normal under the microscope. There is varying degrees of disease in glomerular of obesity mice, and M group is most serious, followed by group T1, group T2 is minor. We can observe the obese mice glomerular bowman’s capsule broadening,thickening of basement membrane,mesangial cell and mesangial matrix proferation,matrix accumulation,lacal thining,and messangial cells,podocyte,epithelial cells with lipid deposition,glomerular volume increased significantly and in part associated with focal segmental glomerulosclerosis in the kidney,in central part of the foot process fusion,mild renal tubular atrophy and interstitial fibrosis. The right kidney weight:The mice’s kidney weight of M group is higher than C group(P<0.01),and T1,T2 is lower than M group and higher than C group(P<0.01), T2 is lower than T1(P<0.01). Glomerular diameter: The mice’s glomerular diameter of M group is bigger than C group(P<0.01),and T1,T2 is smaller than M group and bigger than C group(P<0.01), T2 is smaller than T1(P<0.01). 5.Imumunohistochemical results: The mice’s the level of expression of ZO-1, percentage of podocytes which is signed with WT-1,the level of expression of Adipo R1 of M group is lower than C group,and T1,T2 is higher than M group and lower than C group(P<0.01), T2 is higher than T1(P<0.01). 6.result of software analysis are as follow: the mice’s serum ADP is in negative correlations with body weight, right kidney weight, glomerular diameter and urine m ALB(P<0.001),at the same time it is in positive correlations with the level of expression of Adipo R1 and ZO-1, percentage of podocytes which is signed with WT-1(P<0.001).The mice’s urine m ALB is in positive correlations with body weight, right kidney weight and glomerular diameter(P<0.001),at the same time it is in negative correlations with the level of expression of Adipo R1 and ZO-1, percentage of podocytes which is signed with WT-1(P<0.001). The mice’s level of expression of Adipo R1 is in negative correlations with body weight,right kidney weight and glomerular diameter(P<0.001),at the same time it is in positive correlations with the level of expression of ZO-1, percentage of podocytes which is signed with WT-1(P<0.001).Conclusions: 1.Obese will lead lower serum ADP and less Adipo R1, which leads level of expression of ZO-1 become lower, destabilize the structure of podocytes, damage the kidney. 2. Pioglitazone can effectively improve the level of expression of Adipo R1, make more ADP, reduce proteinuria excretion, improve renal pathological abnormalities caused by obesity. 3. There is correlation between PPARγ agonist and renal pathological abnormalities’ improving.Compared to low-dose PPARγ agonists,high doses pioglitazone treatment can effectively improve ORG.