Effects Of Metformin On Expressions Of T-cadherin In Theliver Tissues Of Rats With Non-alcoholic Fatty Liver Disease

Background and aim:Non-alcoholic fatty liver disease(NAFLD) is a common liver disease with disorder of hepatic lipid metabolism, and it is closely associated with obesity and insulin resistance. Adiponectin is a cytokine secreted by adipose tissue, regulating glucose and lipid metabolism. The biological effects of adiponectin are mediated by its receptors; and T-cadherin is a new found receptor of adiponectin. Whether T-cadherin plays a role in the pathogenesis of NAFLD is still unclear. In this study, we aimed to investigate the hepatic expressions of T-cadherin and effects of metformin on expressions of T- cadherin in rats with NAFLD.Methods: Forty male Sprague-Dawley rats were randomly divided into 5 groups, NC1 group: rats were fed a normal diet for eight weeks, NC2 group: rats were fed a normal diet for sixteen weeks, HFD1 group: rats were fed a high-fat diet for eight weeks, HFD2 group: rats were fed a high-fat diet for sixteen weeks, HFD+M group: rats were fed a high-fat diet for eight weeks and then continued to be fed a high-fat diet meanwhile treated with metformin for eight weeks. T-cadherin protein expression levels in liver tissues were detected with immunohistochemistry, and the T-cadherin m RNA expression levels in livers were detected with fluorescent quantitative PCR.Results: Compared with the HFD2 group, the hepatic steatosis and ballooning degeneration had been alleviated in the HFD+M group. The NAS(nonalcoholic fatty liver disease active score) of the liver tissue in the HFD+M group was significantly lower than that in the HFD2 group(5.33±0.82 vs 6.57±0.79,P<0.01). The protein and m RNA expression levels of T-cadherin in the liver tissues of HFD1 group rats were significantly higher than those of NC1 group rats(6.18±2.42 vs 2.38±0.90 and 1.50±0.31 vs 1.00±0.00,P<0.01 respectively). Compared with NC2 group, the T-cadherin protein expression levels(2.86±0.70 vs 10.39±1.19, P<0.001) and m RNA expression levels(0.94±0.19 vs 3.07±0.41, P<0.001) in the liver tissues of HFD2 group were both distinctly increased. In contrast to HFD1 group, both the T-cadherin protein expressions(6.18±2.42 vs 10.39±1.19,P<0.001) and m RNA expressions(1.50±0.31 vs 3.07±0.41,P<0.001) of HFD2 group were futher increased. Protein and m RNA expressions of T-cadherin in liver tissues decreased in HFD+M group compared with HFD2 group(7.83±2.23 vs 10.39±1.19; 2.56±0.43 vs 3.07±0.41, P<0.05 respectively). The immunohistochemistry scores of the T-cadherin in the liver tissues were positively related to the grade of inflammation(r=0.681,P<0.01), percentage of fat(r=0.837,P<0.01)and ballooning degeneration( r=0.785,P<0.01).Conclusions: The expressions of T-cadherin in the liver tissues increased in the progression of NAFLD, and the expression levels of the T-cadherin were positively related to the grade of liver inflammation, percentage of fat and ballooning degeneration. It indicated that T- cadherin may play a role in the pathogenesis of NAFLD. Metformin treatment alleviated the histological lesions of NAFLD and the hepatic expressions of T-cadherin decreased after metformin treatment. It suggested that metformin may play the therapeutic effect on NAFLD by down-regulating the expression of T- cadherin in the liver tissue.