Efeito do extrato da casca de uva Vitis vifinera nas alterações metabólicas hepáticas em camundongos C57BL/6 submetidos à dieta hiperlipídica

Abstract

The prevalence of obesity over the past decades has shown rapid rise worldwide and is considered an important public health problem. Recent studies from our group have shown that the hydro-alcoholic grape skin extract (ACH09) rich in polyphenols lowers blood glucose in experimental model of diabetes induced by alloxan, and increases the expression of the insulin signaling cascade proteins in skeletal muscle. Thus, the aim of this study was to evaluate the beneficial effects of preventive treatment with ACH09 on metabolic disorders observed in an experimental model of obesity. Male mice C57BL/6 at 30 days of age were separated in four groups and received the following diets for 12 weeks. The Control group: standard diet; ACH09 group: standard diet + 200 mg/kg/day orally; hyperlipidic group (HF): diet with 60% fat and hyperlipidic group + ACH09 (HF + ACH09): diet with 60% fat + 200 mg/kg/day orally. We also determined the food intake, body weight, the mass of visceral fat, plasma levels of total cholesterol, triglycerides, glucose and insulin, and hepatic levels of cholesterol, triglycerides, glycogen and nitrite. Expression of insulin receptor (IR), PI3-K, pAKT, Glut 2, proteins involved in the synthesis of fatty acids and cholesterol (AMPK, pAMPK, HMG-CoA reductase, FAS, SREBP-1c, pACC), as well as the expression of proteins involved in the excretion of cholesterol (ABCG5 and ABCG8 transporters) were evaluated in liver homogenates by western blotting. Hepatic oxidative damage was also determined by lipid peroxidation and carbonyl protein, and the antioxidant enzyme activities (SOD), (CAT) and (GPx) were evaluated by spectrophotometry. was increased, The food intake, body weight and the mass of visceral fat were increased in the HF group, as well as, the plasma and liver cholesterol and triglycerides associated with the development of hepatic steatosis which were reduced by treatment with ACH09. Plasma levels of glucose and insulin resistance were increased in HFgroup and reduced by treatment with ACH09. These findings correlated with reduced expression of insulin signaling cascade proteins in the HF group and increased by treatment with ACH09. The liver glycogen content was reduced HF in and increased in HF+ ACH09. Increased lipogenesis in the HF group was characterized by the increased expression of SREPB-1c and AMPK proteins and reduction of pAMPK and pACC proteins without changing the HMG-CoA reductase and FAS expressions. The treatment with ACH09 reduced the expression of protein-1c SREPB and increased pAMPK expression without changing pACC. Moreover, the extract ACH09 increased the expression of ABCG5 and ABCG8 transporters and showed an antioxidant effect in hepatic tissue by decreasing the formation of malondialdehyde and carbonyl protein and increasing the antioxidant activities enzymes. In conclusion, the ACH09 can modulate the expression of the insulin signaling pathway proteins, as well as the proteins involved in lipogenesis, and excretion of cholesterol preventing the development of hepatic steatosis. The synthesis of NO, the antioxidant action and the increase in insulin sensitivity may exert a central role in ACH09 effects.