Abstract
Resveratrol is a natural polyphenolic stilbene derivative found in several human diet components that possess important and wide-ranging effects in biological systems including anticancer, anti-inflammatory, antioxidant, cardio-protective, and anti-ageing actions and beneficial properties against metabolic diseases. This study addresses the effects of long-term administration of resveratrol on several functional alterations arising from the metabolic syndrome experimental model of obese Zucker rats, and the possible mechanisms involved. The high plasma concentrations of triglycerides, total cholesterol, free fatty acids, insulin and leptin found in obese Zucker rats were reduced in obese rats that received resveratrol. Furthermore, the elevated hepatic lipid content was significantly lower in obese rats treated with resveratrol, an effect which was related to the increased phosphorylation of 5′-AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in the liver of these animals. Resveratrol treatment also improved the inflammatory status peculiar to this model, as it increased the concentration of adiponectin and lowered tumor necrosis factor-α production in the visceral adipose tissue (VAT) of obese Zucker rats. Moreover, chronic intake of resveratrol enhanced VAT eNOS expression among obese Zucker rats. These effects parallel the activation of AMPK and inhibition by phosphorylation of ACC in this tissue. The raised systolic blood pressure and reduced aortic eNOS expression found in obese Zucker rats were significantly improved in the resveratrol-treated obese rats. In conclusion, resveratrol improved dyslipidemia, hyperinsulinemia, hyperleptinemia and hypertension in obese Zucker rats, and produced anti-inflammatory effects in VAT, effects that seem to be mediated by AMPK activation.
Highlights
Type 2 diabetes and obesity are pathologies with a high prevalence in Western societies.Metabolic syndrome is a constellation of several specific abnormalities including abdominal ip t obesity, insulin resistance, dyslipidemia and hypertension [1]
Resveratrol treatment was associated with a significantly lower content of abdominal fat (P < 0.01 vs. obese control rats group (OC)), while no effects were observed in the lean rats (Table 1)
Oral administration of resveratrol to obese Zucker rats for 8 weeks reduces dyslipidemia, hyperinsulinemia, and hyperleptinemia that feature this experimental model. Such effects were accompanied by a reduction in the inflammatory status characteristic of this model, while an increase in 5’-AMP-activated protein kinase (AMPK) activity was found in the liver and VAT of obese rats treated with resveratrol
Summary
Metabolic syndrome is a constellation of several specific abnormalities including abdominal ip t obesity, insulin resistance, dyslipidemia and hypertension [1]. It is directly associated with an increased risk of developing cardiovascular diseases [2, 3], which are the major causes of cr premature mortality in type 2 diabetes patients. Managing the disorders clustered in this syndrome is of great relevance to prevent and to reduce the risk of all of these pathologies. Obesity and insulin resistance have recently been linked to a low-grade chronic inflammatory response characterized by increased macrophage infiltration, altered cytokine production, and activation of the inflammatory d signalling pathway in adipose tissue. Pharmacological agents and natural products able te to reduce inflammatory activity possess anti-diabetic properties
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