Changes of caveolin-1 in the livers of mice with nonalcoholic fatty liver disease caused by high-fat diet

Abstract

Objective To explore the role of caveolin-1 in nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet.Methods A total of 12 ten-week-old male C57BL/6 mice were fed with high-fat and high-cholesterol diet for 14 weeks to establish the NAFLD animal model.And six syngeneic mice fed with normal diet at the same time were taken as control.All the mice were sacrificed by the end of 14th week,body weight,liver weight and the changes of serum lipids of the two groups were compared.The changes of caveolin-1 at mRNA and protein levels in the liver of mice with NAFLD were detected by quantitative polymerase chain reaction (qPCR) and Western blot.The liver steatosis of the mice was observed under light microscopy after stained by hematoxylin and eosin.The changes of distribution of caveolin-1 in liver were examined by immunohistochemistry.The differences of caveolin-1 at mRNA and protein level in livers between the two groups were compared by t test.The differences of immunohistochemical scores of caveolin-1 expression in the livers of mice with different degree of fatty liver were analyzed by ordinal variables of two independent samples ranksum test analysis.Results After 14 weeks high-fat and high-cholesterol diet,all the mice of experiment group developed NAFLD.Nine of which were severe and three were moderate.Compared with the control group,serum total cholesterol,high density lipoprotein cholesterol and low density lipoprotein cholesterol of experiment group significantly increased ((1.940 ± 0.300) mmol/L vs (3.771±0.800) mmol/L,(1.120±0.066) mmol/L vs (2.224±0.420) mmol/L,(0.510±0.191) mmol/L vs (1.241±0.660) mmol/L,t=-3.760,-5.474,-3.332,all P＜0.01),however there was no significant difference in triglyceride (P＞0.05).The caveolin-1 of experiment group significantly increased at mRNA (1.536 ±0.226 vs 0.980± 0.272,t=3.371,P＜0.05) and protein levels (0.643±0.240 vs 0.100±0.130,t=4.847,P＜0.01).The immunohistochemical results indicated that the increased caveolin-1 expression mainly distributed in the membrane of hepatocytes,cytoplasm and membrane of lipid droplets.Conclusion The up-regulated caveolin-1 expression in the livers of NAFLD mice induced by high-fat and high-cholesterol may be involved in the mechanism of NAFLD. Key words: Caveolin 1 ; Fatty liver; Hyperlipidemias; Cholesterol, dietary; Mice, inbred C57BL