Therapeutical Effect Of Resveratrol On The Nonalcoholic Fatty Liver Disease Rat Model And Its Potential Mechanism

Non-alcoholic fatty liver (NAFLD) is a kind of liver disease with the pathological features liver steatosis and fat piling up without excess alcohol intake or other risk factors. The pathogenesis of NAFLD has not been fully elucidated, and there is no fundamental treatment yet. The anorectic molecule nesfatin-1 was first described to induce dose-dependent anorexigenic effects, and increasing evidence demonstrated its effect on the glucose and lipid metabolism. However, it remains unclear whether nesfatin-1 play a role in the pathogenesis of NAFLD. Resveratrol (RES) is a kind of phenolic compoundswith intensive inflammantory and antioxidant effect, and its liver-protection effects has also been demonstrated in animal studies. In the present study, the NFALDe rat model was induced by high-fat diet, and the role of nesfatin-1 in its pathogenesis and the therapeutic effect of RES were explored.Objective:To investigate the change of plasma nesfatin-1 concentration and glucose and lipid metabolism in a NAFLD rat model induced by high-fat diet, and explore effect the therapeutic effect of RES on NAFLD rat model and the potential mechanism.Methods:1. Establishment of the nonalcoholic fatty liver disease (NAFLD) rat model via high-fatdietThe nonalcoholic fatty liver disease rat model was established through introduction of a high-fat diet, and four weeks later, the intraperitoneal glucose tolerance test was conducted.Serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique. The plasma levels of nesfatin-1, leptin, and insulin (INS) were measured via enzyme-linked immunosorbent assay (ELISA), the histological changes of the liver was observed via hematoxylin and eosin (HE) staining, and the protein expressions of β-catenin, p-β-catenin and cyclinD1 in the liver were detected using western blot and compared with β-actin.2. Therapeutic effect of Res on NAFLD rat model and the potential mechanism 45 male adult SD rats were devided randomly into 5 groups including the control group, the NAFLD model group, the RES (15mg/kg) treated group, the sitagliptin (10mg/kg) treated group, and the rosiglitazone (5mg/kg) treated group. Rats in the control group received standard diet, and the other rats received the high-fat diet.4 weeks later, the treated rats were given the corresponding drugs with the given dose, while the rats in the control and the model group received CMC-Na with the same volume. After 28 consecutive days’treatment, the intraperitoneal glucose tolerance test was conducted. Serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique. The plasma levels of nesfatin-1, leptin, and insulin (INS) were measured via enzyme-linked immunosorbent assay (ELISA), the histological changes of the livers was observed via HE staining.Results:1. The bodyweight, liver weight, liver index, and area under the curve of the intraperitoneal glucose tolerance test were all higher in the model rats than those in the controls. Compared with the control,serum concentrations of ALT, TBIL, IBIL, TC, LDL-C in the model rats were all increased. The plasma nesfatin-1 level was increased in model rats while the plasma concentrations of leptin and insulin were decreased, and a negative correlation was found between the plasma concentration of nesfatin-1 and leptin. Inflammation and hepatocyte steatosis were detected in the livers of model rats, and the protein expression of cyclinD1 was upregulated while the phosphorylation of P-catenin was decreased in the livers of the model rats.2. Compared with the control, NAFLD rats showed increased bodyweight, liver weight, liver index, area under the curve of the intraperitoneal glucose tolerance test, and serum concentrations of ALT, TBIL, IBIL, TC, LDL-C, and nesfatin-1. However, all these changes were reversed after treatment of RES (15mg/kg). Moreover, RES (15mg/kg) could improve the inflammation and hepatocyte steatosis in NAFLD rats.Conclusion:1. Post-creation of nonalcoholic fatty liver disease rat models through high fat diets, changes were observed in plasma nesfatin-1 concentration, perhaps a vital part of glucose and lipid metabolism dysfunction.2. RES could alleviate the dysfunction of the glucose and lipid metabolism and the liver inflammation in NAFLD rats, the mechanism of which might be involved in its downregulation of the plasma nesfatin-1 concentration.