The protective effects of rosiglitazone on tree shrew’s fatty liver

Objective To investigate the effects of rosiglitazone on tree shrew's fatty liver induced by high sugar and fat diet. Methods Thirty six tree shrews were assigned as the chow diet group (group A, 8 animals) and the high sugar and high fat fed group (28 animals). The latter were fed alternately with the mix food containing 40% saccharu and 20% fat by one day interval. In the high sugar and high fat fed group, 19 animals (67.86%), which had an increased FBG level equal to or more than 11.1 mmol/L 22 weeks after the diet, were divided into 2 subgroups: rosiglitazone supplemented group (group B), to which rosiglitazone was added at a dose of 5 mg·kg -1 ·d -1 for seven weeks, and non supplemented group (group C). Body weight, fasting serum insulin(FINS) and blood lipid including total cholesterol(TC), triglyceride (TG), high density lipoprotein cholesterol (HDL C) and low density lipoprotein cholesterol (LDL C) were examined during the experiment. Liver biopsies were carried out under general anaesthesia at 22 week and the end of the experiment in all animals. The samples of liver were fixed in 4% polymerisatum for 12 h, then through pathological routine processing. The expressions of uncoupling protein 3 (UCP3) and insulin receptor (IR) were analyzed by calculating the UCP3 and IR expressing positive cells and by analyzing the area density of positive cells using computer aided video system. Results Morphological alteration under light microscopy showed that all animals from both group B and C had a typical steatosis throughout the liver sections 22 week after high sugar and high fat feeding. The area density of steatosis and the proportion of involved hepatocytes were approximately 30% and reached higher degrees in group C ( P 0.05) at 29 week, while those in group B reduced markedly by more than 90%( P 0.01) after administration of rosiglitazone. A smaller proportion of hepatocytes from group C (27.6%±4.9%, P 0.01) was positive for UCP3 by immunohistochemistry, compared with group B (57.71%±19.2%). The expression level of UCP3 protein in liver was correlated reversely with both the area density of hepatosteatosis ( r = -0.86 , P 0.01) and the proportion of steatosis cells( r = -0.79 , P 0.01). In group C, the expression level of IR β in the liver was higher than that of controls ( P 0.05), and there was an increased blood level of TC in group C compared with its baseline ( P =0.33) as well as with group B ( P =0.01) and pure increased values of TG compared with group B ( P 0.05) at the end of the trial. As for group B, no significant changes were observed in the values of blood lipids. FBG increased progressively with time in group B and C, from 13 week after the experiment to 22 week of peak levels (FBG≥11.1 mmol/L). In the end of the experiment (29 week), group B had a lower blood glucose level than group C ( P 0.05), while the values of FBG were significantly higher in group C than in both grouup A and B (all P 0.05). Group C also had a greater value of FINS and more homoestasis model assessment of insulin resistance (HOMA IR) than group A and B (all P 0.05), while there were no significant differences of FINS and HOMA IR between group B and group A (all P 0.05) .Conclusion Increased expression of liver for IR β in tree shrews on a high sugar and high fat diet indicates that insulin signaling may have a role in the development of hepatosteatosis.