RESUMO
We hypothesized that a polyphenol-rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high-fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. 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. 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. 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 anti-inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF-α, 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 as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Antocianinas/farmacologia , Músculo Esquelético/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Vitis/química , Adiponectina/sangue , Tecido Adiposo/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Peso Corporal , Dieta Hiperlipídica , Frutas/química , Transportador de Glucose Tipo 4/metabolismo , Inflamação/tratamento farmacológico , Insulina/sangue , Resistência à Insulina , Interleucina-6/metabolismo , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Polifenóis/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Nonalcoholic fatty liver disease is one of the most common complications of obesity. The Vitis vinifera L. grape skin extract (ACH09) is an important source of polyphenols, which are related to its antioxidant and antihyperglycemic activities. We hypothesized that ACH09 could also exert beneficial effects on metabolic disorders associated with obesity and evaluated ACH09's influence on high-fat (HF) diet-induced hepatic steatosis and insulin resistance in C57BL/6 mice. The animals were fed a standard diet (10% fat, control) or an HF diet (60% fat, HF) with or without ACH09 (200mg/[kg d]) for 12weeks. Our results showed that ACH09 reduced HF diet-induced body weight gain, prevented hepatic lipid accumulation and steatosis, and improved hyperglycemia and insulin resistance. The underlying mechanisms of these beneficial effects of ACH09 may involve the activation of hepatic insulin-signaling pathway because the expression of phosphorylated insulin receptor substrate-1, phosphatidylinositol 3-kinase, phosphorylated Akt serine/threonine kinase 1, and glucose transporter 2 was increased by ACH09 and correlated with improvement of hyperglycemia, hyperinsulinemia, and insulin resistance. ACH09 reduced the expression of the lipogenic factor sterol regulatory-element binding protein-1c in the liver and upregulated the lipolytic pathway (phosphorylated liver kinase B1/phosphorylated adenosine-monophosphate-activated protein kinase), which was associated with normal hepatic levels of triglyceride and cholesterol and prevention of steatosis. ACH09 prevented the hepatic oxidative damage in HF diet-fed mice probably by restoration of antioxidant activity. In conclusion, ACH09 protected mice from HF diet-induced obesity, insulin resistance, and hepatic steatosis. The regulation of hepatic insulin signaling pathway, lipogenesis, and oxidative stress may contribute to ACH09's protective effect.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/prevenção & controle , Resistência à Insulina , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vitis/química , Animais , Antioxidantes/farmacologia , Colesterol/sangue , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Fígado Gorduroso/tratamento farmacológico , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 2/metabolismo , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Lipogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Polifenóis/farmacologia , Triglicerídeos/sangue , Quinase Ativadora de Quinase Dependente de CiclinaRESUMO
Previously, we have demonstrated that the seeds of Euterpe oleracia Mart. (açaí) are rich in polyphenols with antihypertensive and antioxidant properties. This study evaluated the renal protective effects of the hydroalcoholic extract obtained from the seeds of açaí (ASE) fruits in two-kidney, one-clip (2K1C) renovascular hypertension. Young male Wistar rats were used to obtain 2K1C and sham groups. Animals received ASE (200 mg/(kg·day) in drinking water) or vehicle for 40 days. We evaluated serum and urinary parameters, renal structural changes, and oxidative status. The increase in systolic blood pressure of the 2K1C group was accompanied by a decrease in left kidney volume and number of glomeruli, as well as an increase in glomerular volume and collagen deposition. ASE prevented the alterations of these parameters, except the reduced kidney volume. Serum levels of urea and creatinine and urinary protein excretion were increased in the 2K1C group and treatment with ASE improved all these functional parameters. The increased oxidative damage in the 2K1C group, assessed by lipid and protein oxidation, was prevented by ASE. The nitrite content and both expression and activity of antioxidant enzymes (superoxide dismutase-1, catalase, and glutathione peroxidase) were lower in the 2K1C group and restored by ASE. ASE substantially reduced renal injury and prevented renal dysfunction in 2K1C rats probably through its antihypertensive and antioxidant effects, providing a natural resource for treatment and prevention of renovascular hypertension-related abnormalities.
Assuntos
Anti-Hipertensivos/administração & dosagem , Euterpe/química , Hipertensão Renovascular/tratamento farmacológico , Rim/irrigação sanguínea , Extratos Vegetais/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Catalase/metabolismo , Humanos , Hipertensão Renovascular/metabolismo , Hipertensão Renovascular/fisiopatologia , Rim/lesões , Rim/metabolismo , Rim/fisiopatologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Sementes/química , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVES: This study examined the effect of açaí (Euterpe oleraceaâ Mart.) seed extract (ASE) on cardiovascular and renal alterations in adult offspring, whose mothers were fed a low-protein (LP) diet during pregnancy. METHODS: Four groups of rats were fed: control diet (20% protein); ASE (200 mg/kg per day); and LP (6% protein); LP + ASE (6% protein + ASE) during pregnancy. After weaning, all male offspring were fed a control diet and sacrificed at 4 months old. We evaluated the blood pressure, vascular function, serum and urinary parameters, plasma and kidney oxidative damage, and antioxidant activity and renal structural changes. KEY FINDINGS: Hypertension and the reduced acetylcholine-induced vasodilation in the LP group were prevented by ASE. Serum levels of urea, creatinine and fractional excretion of sodium were increased in LP and reduced in LP + ASE. ASE improved nitrite levels and the superoxide dismutase and glutathione peroxidase activity in LP, with a corresponding decrease of malondialdehyde and protein carbonyl levels. Kidney volume and glomeruli number were reduced and glomerular volume was increased in LP. These renal alterations were prevented by ASE. CONCLUSIONS: Treatment of protein-restricted dams with ASE provides protection from later-life hypertension, oxidative stress, renal functional and structural changes, probably through a vasodilator and antioxidant activity.