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-alpha 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.