Peroxisome proliferator activated receptor-gamma in pathogenesis of experimental fatty liver disease

AIM: To study the expression of peroxisome proliferator activated receptor-gamma (PPARgamma) in the liver of rats with fatty liver disease (FLD) and to explore the role of PPARgamma in the pathogenesis of FLD to provide the basis for using PPARgamma ligand to treat patients with FLD. METHODS: Forty Wistar rats were divided into 4 groups of ten rats each randomly: normal group (group A), alcohol group (group B), fat-rich diet group (group C), alcohol and fat-rich diet group (group D). The rats were sacrificed at the end of the 16th week from the feeding day. Alanine aminotransferase (ALT), tumor necrosis factor-alfa (TNFalpha) in serum and malondialdehyde (MDA) in liver homogenate were determined; livers were collected for observing pathologic changes by HE, Sudan IV, Masson stain under microscope. The morphologic results were analyzed by picture quantitative analysis technique. The changes of ultrastructure were also examined under electron microscope. The expression of PPARgamma in liver was detected by immunohistochemistry and RT-PCR. The correlations between the expression of PPARgamma and biochemical indexes, and liver histology were analyzed. RESULTS: The steatosis, inflammation, necrosis and fibrosis were present in livers of different experimental groups, especially in livers of alcohol and fat-rich diet group. The content of immunodetectable PPARgamma was decreased remarkably in the livers of model rats (group B-D); the level in alcohol and fat-rich diet group (3.43+/-1.48) was significantly lower than that in normal group (18.34+/-3.73), alcohol group (8.82+/-2.52) and fat-rich diet group (11.73+/-2.51) (all P<0.01). The level of PPARgamma mRNA was also lower in the livers of model rats (group B-D) than in livers of controls. The expression of PPARgamma in rat liver correlated negatively with the degree of its inflammation, necrosis and fibrosis, as well as the level of serum TNFalpha and the content of MDA in liver homogenates, but not with steatosis or serum ALT. CONCLUSION: Decreased expression of PPARgamma may play an important role in the development of hepatocellular inflammation, necrosis and fibrosis of rats with FLD. Thus, activating PPARgamma by its ligand can be anticipated to provide a therapy target for FLD.