RESUMO
A growing body of evidence suggests a protective role of polyphenols and exercise training on the disorders of type 2 diabetes mellitus (T2DM). We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on diabetic complications induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks and a single dose of STZ (35 mg/kg i.p.). Control (C) and Diabetic (D) animals were subdivided into four groups each: Sedentary, Training, ASE Sedentary, and ASE Training. ASE (200 mg/kg/day) was administered by gavage and the exercise training was performed on a treadmill (30min/day; 5 days/week) for 4 weeks after the diabetes induction. In type 2 diabetic rats, the treatment with ASE reduced blood glucose, insulin resistance, leptin and IL-6 levels, lipid profile, and vascular dysfunction. ASE increased the expression of insulin signaling proteins in skeletal muscle and adipose tissue and plasma GLP-1 levels. ASE associated with exercise training potentiated the reduction of glycemia by decreasing TNF-α levels, increasing pAKT and adiponectin expressions in adipose tissue, and IR and pAMPK expressions in skeletal muscle of type 2 diabetic rats. In conclusion, ASE treatment has an antidiabetic effect in type 2 diabetic rats by activating the insulin-signaling pathway in muscle and adipose tissue, increasing GLP-1 levels, and an anti-inflammatory action. Exercise training potentiates the glucose-lowering effect of ASE by activating adiponectin-AMPK pathway and increasing IR expression.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Euterpe , Hipoglicemiantes/uso terapêutico , Condicionamento Físico Animal , Fitoterapia , Extratos Vegetais/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Glicemia/análise , Terapia Combinada , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/terapia , Dieta Hiperlipídica , Avaliação Pré-Clínica de Medicamentos , Peptídeo 1 Semelhante ao Glucagon/sangue , Hemoglobinas Glicadas/análise , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Insulina/sangue , Resistência à Insulina , Interleucina-6/sangue , Leptina/sangue , Lipídeos/sangue , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Sementes/químicaRESUMO
PURPOSE: Euterpe oleracea Mart. (açaí) seed extract (ASE), through its anti-hypertensive, antioxidant and anti-inflammatory properties, may be useful to treat or prevent human diseases. Several evidences suggest that oxidative stress and inflammation contribute to the pathogenesis of diabetic nephropathy; therefore, we tested the hypothesis that ASE (200 mg/kg-1day-1) prevents diabetes and hypertension-related oxidative stress and inflammation, attenuating renal injury. METHODS: Male rats with streptozotocin (STZ)-induced diabetes (D), and spontaneously hypertensive rats with STZ-induced diabetes (DH) were treated daily with tap water or ASE (D + ASE and DH + ASE, respectively) for 45 days. The control (C) and hypertensive (H) animals received water. RESULTS: The elevated serum levels of urea and creatinine in D and DH, and increased albumin excretion in HD were reduced by ASE. Total glomeruli number in D and DH, were increased by ASE that also reduced renal fibrosis in both groups by decreasing collagen IV and TGF-ß1 expression. ASE improved biomarkers of renal filtration barrier (podocin and nephrin) in D and DH groups and prevented the increased expression of caspase-3, IL-6, TNF-α and MCP-1 in both groups. ASE reduced oxidative damage markers (TBARS, carbonyl levels and 8-isoprostane) in D and DH associated with a decrease in Nox 4 and p47 subunit expression and increase in antioxidant enzyme activity in both groups (SOD, catalase and GPx). CONCLUSION: ASE substantially reduced renal injury and prevented renal dysfunction by reducing inflammation, oxidative stress and improving the renal filtration barrier, providing a nutritional resource for prevention of diabetic and hypertensive-related nephropathy.
Assuntos
Antioxidantes/uso terapêutico , Nefropatias Diabéticas/prevenção & controle , Suplementos Nutricionais , Euterpe/química , Extratos Vegetais/uso terapêutico , Insuficiência Renal/prevenção & controle , Sementes/química , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Apoptose , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Experimental/imunologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Fibrose , Barreira de Filtração Glomerular/imunologia , Barreira de Filtração Glomerular/metabolismo , Barreira de Filtração Glomerular/patologia , Barreira de Filtração Glomerular/fisiopatologia , Hipertensão/complicações , Hipertensão/dietoterapia , Hipertensão/imunologia , Hipertensão/fisiopatologia , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Rim/imunologia , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Estresse Oxidativo , Ratos Endogâmicos SHR , Insuficiência Renal/complicações , Insuficiência Renal/etiologia , Insuficiência Renal/metabolismoRESUMO
Type 2 diabetes mellitus contributes to an increased risk of metabolic and morphological changes in key organs, such as the liver. We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on hepatic steatosis induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks, followed by a single low dose of STZ (35 mg/kg i.p.). Control and diabetic groups were subdivided into four groups that were fed with standard chow diet for 4 weeks. Control (C) group was subdivided into Sedentary C, Training C, ASE Sedentary C and ASE Training C. Diabetic (D) group was subdivided into Sedentary D, Training D, ASE Sedentary D and ASE Training D. ASE (200 mg/kg/day) was administered by intragastric gavage, and the exercise training was performed on a treadmill (30 min/day; 5 days/week). Treatment with ASE associated with exercise training reduced the blood glucose (70.2%), total cholesterol (81.2%), aspartate aminotransferase (51.7%) and hepatic triglyceride levels (66.8%) and steatosis (72%) in ASE Training D group compared with the Sedentary D group. ASE associated with exercise training reduced the hepatic lipogenic proteins' expression (77.3%) and increased the antioxidant defense (63.1%), pAMPK expression (70.2%), cholesterol transporters (71.1%) and the pLKB1/LKB1 ratio (57.1%) in type 2 diabetic rats. In conclusion, ASE treatment associated with exercise training protects against hepatic steatosis in diabetic rats by reducing hepatic lipogenesis and increasing antioxidant defense and cholesterol excretion.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Euterpe/química , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Condicionamento Físico Animal , Extratos Vegetais/farmacologia , Animais , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/complicações , Enzimas/metabolismo , Glicogênio/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Carbonilação Proteica , Proteínas/metabolismo , Ratos Wistar , Sementes/químicaRESUMO
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
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.