Efeitos do extrato da casca de uvas Vitis vinifera nas alterações metabólicas induzidas pela dieta hiperlipídica em camundongos C57BL/6

Abstract

Obesity has been related to an excessive accumulation of adipose tissue, resulting mainly from the imbalance between energy intake and energy expenditure. Functional changes in adipocytes can lead to dyslipidemia, hyperinsulinemia, inflammation and oxidative stress, increasing the risk of cardiovascular diseases, diabetes mellitus, cancer and metabolic syndrome. Previously, we have demonstrated a potential antioxidant and hypoglycemic effect of a polyphenol-rich extract from Vitis vinifera L grape skin (GSE). In the present study, we hypothesized that GSE may exert beneficial effects on obesity and related metabolic disorders induced by a high fat diet (HFD). The animals were fed a standard diet (10% saturated fat, Control and GSE groups) or an HFD (60% saturated fat, HF and HF+GSE groups) with or without GSE (200 mg.kg-1.d-1) for 12 weeks. Food intake and body weight were evaluated periodically and fasting glycemia at days 0, 45 and 90. At the end of the experimental period, the animals were anesthetized (thiopental 30 mg / kg body weight, i.p.), heparinized and blood was collected by cardiac puncture. Plasma levels of the following markers were evaluated: glycated hemoglobin, lipid profile and insulin. Protein expression of insulin signaling cascade (insulin receptor, pIRS, PI3-K, AKT, GLUT4) were analyzed in muscle and adipose tissue, and AMPK and pAMPK in muscle. Plasma levels and expression in the adipose tissue of the inflammatory markers IL-6 and TNF-α, and the adipokines adiponectin and leptin, as well as plasma resistin, were also observed. The evaluation of oxidative damage and the activity of antioxidant enzymes was performed in plasma, muscle and adipose tissue. Our results showed that GSE prevented weight gain, dyslipidemia, insulin resistance, the alterations in plasma levels of leptin, adiponectin and resistin, and the deregulation of leptin and adiponectin expression in adipose tissue. The possible mechanisms of these beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio and GLUT4 expression in muscle and adipose tissue from HFD fed mice. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an antiinflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNFα and IL-6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF fed mice by regulating insulin sensitivity and GLUT4 expression, and preventing the oxidative stress, and inflammation in skeletal muscle and adipose tissue.