Effects Of Rosiglitazone On The Expression Of PPARγ And UCP2 In The Liver Of Rats With Nonalcoholic Fatty Liver Disease

Objectives: To establish a model of nonalcoholic fatty liver disease(NAFLD) rat fed with high fat diet. To investigate the role of peroxisome proliferator-activated receptor gamma(PPARγ) and uncoupling protein-2(UCP2) in the development of NAFLD, and explore the effect of rosiglitazone(RSG) on NAFLD.Methods: Sixty male SD rats were randomly divided into normal control group(C group), model group fed with high fat diet(M group), low dosage rosiglitazone treated group(TL group) and high dosage rosiglitazone treated group(TH group). C group and M group have three time points: feeding for 4, 8 and 12 weeks. TL group and TH group have two time points: feeding for 8 and 12 weeks, 6 ones at each time point. Check on the weight of rats weekly. The levels of serum TC, TG, AST, ALT, GLU and liver homogenate TC, TG, GLU were measured by biochemical method. Liver histopathologic evaluation was performed by hematoxylin-eosin staining. The expression of PPARγand UCP2 in the liver were detected by immunohistochemistry and semi-quantitative RT-PCR.Results: (1) The body weight was greatly increased in M group than in C group(P<0.05). Administration of rosiglitazone could significantly increased the weight (P<0.05). The liver index (the ratio of wet weight of liver to body weight) was increased in M group (P<0.05), and intensified over time. Rosiglitazone could greatly diminish the liver index in time and dose-dependent way.(2) The levels of serum TC, TG, AST and ALT were significantly higher in M group than in C group, especially at week 12(P<0.05). Administration of rosiglitazone could greatly decrease the levels in time and dose-dependent way. The levels of liver homogenate TC and TG were significantly higher in M group than in C group (P<0.05). Rosiglitazone could greatly decrease liver homogenate TG (P<0.05), especially in TH group, but TC was not significantly decreased (P>0.05). The differences of blood glucose and liver homogenate glucose between each group were not significant (P>0.05).(3) There were diffusive hepatic steatosis in the model group while negative in the normal control group (P<0.01). The severity of fatty liver was associated with duration of high fat diet. Rosiglitazone significantly attenuated the pathological changes in the liver, especially in TH group (P<0.05).(4) The hepatic expression of UCP2 protein was progressively increased in M group at 4, 8 and 12 week (P<0.05), and was significantly higher than C group. Compared with M group, it was significantly reduced in TL group and TH group (dose dependent) ( P<0.05).(5) Compared with C group, the hepatic mRNA expression of PPARγand UCP2 increased significantly over time in M group (P<0.05). Compared with M group, they were greatly reduced in TL group and TH group (time and dose dependent) (P<0.05), but still higher than C group at the same time point (P<0.05). (6) The gene expression of PPARγwas positively correlated with the expression of UCP2(r=0.736, P<0.01).Conclusions: The rat model of NAFLD can be established successfully by feeding with high fat diet. PPARγand UCP2 were up-regulated in the livers of NAFLD rats. Rosiglitazone seems to be effective to improve hepatic steatosis in time and dose- dependent way. Rosiglitazone can inhibit the expression of PPARγand UCP2, these may be contribute to the effect.