The Influence Of Ursodeoxycholic Acid On Hepatic Lipid Deposition And Pancreatic Islet Function In High-fat Diet-fed Rats

Objective:Investigate the effects of Ursodeoxycholic Acid on Hepatic Lipid Deposition and Pancreatic Islet Function in High-fat Diet-fed rats.Methods:Divide SD rats into 3 groups,Group A(normal group,n=6),Group B(high-fat group,n=6),and Group C(high-fat+intervention group,n=6).The rats in group A were fed with normal diets,rats in group B and C were fed with high fat diets,and the rats in group C were fed with ursodeoxycholic acid in the meantime(0.25%of food intake,once daily by gavage)for 8 weeks.After 8 weeks,serum AST,ALT,AKP,GGT,TC,TG,LDL-C and body weights were measured,oral glucose tolerance test(OGTT),C-peptide release test,and insulin release test were performed,at the end of 8 weeks,the rats were euthanized under anestesia,liver and pancreas tissues were collected,liver TG,TC content were measured,HE staining and Masson staining were performed to observe liver and pancreas pathological changes.Results:1、Body weight:Compared with group A,body weight in groups B were increased significantly.Compared with group B,body weight in group C changed sightly.2、OGTT:OGTT,insulin release test,and C-peptide release test:2-hour postprandial blood glucose levels in group B were significantly higher than those in group A(P<0.05),while group C showed a significant decrease in 2-hour postprandial blood glucose levels compared to group B(P<0.05).Fasting and 2-hour postprandial insulin levels in group B were higher than those in group A(P<0.05),and fasting and 2-hour postprandial insulin levels in group C were significantly lower than those in group B(P<0.05).Fasting and2-hour postprandial C-peptide levels in group B were higher than those in group A(P<0.05),and 2-hour postprandial insulin levels in group C were significantly lower than those in group B(P<0.05).Compared with group A,the AUC_Gin group B was significantly increased(P<0.05),while there were no significant changes in AUC_Iand AUC_C.In contrast,compared with group B,group C had significantly reduced AUC_Gand AUC_I.3、Liver enzymes:The levels of ALT,AST,GGT,and ALP in group B were significantly higher than those in group A(P<0.05).The levels of ALT,AST,and GGT in group C were significantly lower than those in group B(P<0.05).4、Blood lipids:The TG levels in group B were significantly higher than those in group A(P<0.05).The levels of TG and TC in group C were improved compared with those in group B(P<0.05).5、Hepatic TG and TC:Both hepatic TG and TC levels in group B were significantly increased compared with those in group A(P<0.05).Hepatic TG levels in group C were significantly lower than those in group B(P<0.05).6、Liver pathology:Compared with group A,the liver in group B showed varying degrees of fatty degeneration,hepatocyte swelling,inflammatory cell infiltration,and fibrosis.Compared with group B,group C showed reduced fatty degeneration,alleviated hepatocyte swelling,decreased inflammatory cell infiltration,and decreased fibrosis.7、Pancreatic pathology:Compared with group A,the pancreas in group B showed an increased area of islet,morphological changes,and fibrosis.In contrast,compared with group B,group C showed a reduction in the area of islet,morphology closer to normal,and reduced fibrosis.Conclusion:UDCA intervention can lead to a decrease in serum TG,TC,and liver TG levels in rats fed with high fat diets,reverse fatty degeneration,alleviate fibrosis,and significantly reduce liver enzyme levels.Moreover,UDCA intervention can ameliorate insulin resistance,repair islets,and decrease blood glucose levels.