RESUMEN
High adipose tissue (AT) accumulation in the body increases the risk for many metabolic and chronic diseases. This work investigated the capacity of the flavonoid (-)-epicatechin to prevent undesirable modifications of AT in mice fed a high-fat diet. Studies were focused on thoracic aorta perivascular AT (taPVAT), which is involved in the control of blood vessel tone, among other functions. Male C57BL/6J mice were fed for 15 weeks a high-fat diet with or without added (-)-epicatechin (20 mg per kg body weight per d). In high-fat diet fed mice, (-)-epicatechin supplementation: (i) prevented the expansion of taPVAT, (ii) attenuated the whitening of taPVAT (according to the adipocyte morphology, diameter, and uncoupling-protein 1 (UCP-1) levels) and (iii) blunted the increase in plasma glucose and cholesterol. The observed taPVAT modifications were not associated with alterations in the aorta wall thickness, aorta tumor necrosis factor-alpha (TNF-α) and NADPH-oxidase 2 (NOX2) expression, and endothelial nitric oxide synthase (eNOS) phosphorylation levels. In summary, our results indicate (-)-epicatechin as a relevant bioactive protecting from the slow and silent development of metabolic and chronic diseases as they are associated with excessive fat intake.
Asunto(s)
Tejido Adiposo/patología , Aorta Torácica/patología , Catequina/farmacología , Dieta Alta en Grasa/efectos adversos , Grasas de la Dieta/efectos adversos , Suplementos Dietéticos , Extractos Vegetales/farmacología , Adipocitos/metabolismo , Adipocitos/patología , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco , Animales , Aorta Torácica/metabolismo , Glucemia/metabolismo , Catequina/uso terapéutico , Colesterol/sangre , Grasas de la Dieta/administración & dosificación , Masculino , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/patología , Enfermedades Metabólicas/prevención & control , Ratones Endogámicos C57BL , NADPH Oxidasa 2/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Obesidad/metabolismo , Obesidad/prevención & control , Extractos Vegetales/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , Proteína Desacopladora 1/metabolismoRESUMEN
This study investigated the effects of a quercetin-supplemented diet on the biochemical changes installed in the heart of NO-deficient rats in terms of oxidants production and NO bioavailability determinants. Sprague-Dawley rats were subjected to Nω-nitro-l-arginine methyl ester (l-NAME) treatment (360â¯mg/L l-NAME in the drinking water, 4â¯d) with or without supplementation with quercetin (4â¯g/kg diet). l-NAME administration led to increased blood pressure (BP) (30%), decreased nitric oxide synthase (NOS) activity (50%), and increases in NADPH oxidase (NOX)-dependent superoxide anion production (60%) and p47phox protein level (65%). The co-administration of quercetin prevented the increase in BP and the activation of NOX but did not modify the decrease in NOS activity caused by l-NAME. In addition, quercetin affected oxidative stress parameters as glutathione oxidation, and the activities of oxidant detoxifying enzymes superoxide dismutase, glutathione peroxidase, and catalase. Thus, quercetin administration counteracts l-NAME effects on NO bioavailability determinants in vivo, essentially through controlling NOX-mediated superoxide anion production.
Asunto(s)
Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Quercetina/farmacología , Animales , Antioxidantes/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Glutatión/metabolismo , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/prevención & control , Masculino , NG-Nitroarginina Metil Éster/administración & dosificación , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Quercetina/administración & dosificación , Ratas Sprague-Dawley , Superóxidos/metabolismoRESUMEN
The aim of this work was to evaluate the effects of (-)-epicatechin administration in the heart of a rat model with reduced NO production that follows a short-term treatment with L-NAME. Sprague-Dawley rats were treated for 4 d with L-NAME in the absence or presence of (-)-epicatechin in the diet. The redox status in cardiac tissue was improved by (-)-epicatechin administration. L-NAME treatment induced a decrease in NO synthase activity (-62%, p<0.05) and an increase in NADPH-dependent superoxide anion production (+300%, p<0.05) that were totally prevented by (-)-epicatechin administration. These effects of (-)-epicatechin were associated with a higher endothelial NO synthase phosphorylation at an activation site and a reduced expression of the regulatory subunit, p47(phox), suggesting the involvement of posttranslational mechanisms in (-)-epicatechin action. Thus, the (-)-epicatechin treatment would restore NO steady state levels in vivo through effects on both, its synthesis and degradation via the reaction with superoxide anion. The fact that (-)-epicatechin is commonly present in human diet makes this compound a reasonable explanation for the positive cardiovascular effects of a high consumption of fruits and vegetables.
Asunto(s)
Antihipertensivos/uso terapéutico , Catequina/uso terapéutico , Modelos Animales de Enfermedad , Ventrículos Cardíacos/enzimología , Hipertensión/prevención & control , NADPH Oxidasas/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Animales , Vasos Coronarios/enzimología , Vasos Coronarios/metabolismo , Suplementos Dietéticos , Activación Enzimática , Frutas/química , Ventrículos Cardíacos/metabolismo , Hipertensión/enzimología , Hipertensión/metabolismo , Masculino , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/genética , NG-Nitroarginina Metil Éster , Óxido Nítrico/agonistas , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/química , Fosforilación , Procesamiento Proteico-Postraduccional , Distribución Aleatoria , Ratas Sprague-Dawley , Estereoisomerismo , Superóxidos/antagonistas & inhibidores , Superóxidos/metabolismo , Verduras/químicaRESUMEN
Increasing evidence indicates that several mechanisms, associated or not with antioxidant actions, are involved in the effects of flavonoids on health. Flavonoid-rich beverages, foods, and extracts, as well as pure flavonoids are studied for the prevention and/or amelioration of metabolic syndrome (MS) and MS-associated diseases. We summarize evidence linking flavonoid consumption with the risk factors defining MS: obesity, hypertriglyceridemia, hypercholesterolemia, hypertension, and insulin resistance. Nevertheless, a number of molecular mechanisms have been identified; the effects of flavonoids modifying major endpoints of MS are still inconclusive. These difficulties are explained by the complex relationships among the risk factors defining MS, the multiple biological targets controlling these risk factors, and the high number of flavonoids (including their metabolites) present in the diet and potentially responsible for the in vivo effects. Consequently, extensive basic and clinical research is warranted to assess the final relevance of flavonoids for MS.