Rivera Leonor, Morón Rocío, Zarzuelo Antonio, Galisteo Milagros
Department of Pharmacology, CIBER-EHD, CTS-164 Research Group, School of Pharmacy, University of Granada, Campus Universitario Cartuja s/n, 18071 Granada, Spain.
Biochem Pharmacol. 2009 Mar 15;77(6):1053-63. doi: 10.1016/j.bcp.2008.11.027. Epub 2008 Dec 3.
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.
白藜芦醇是一种天然多酚芪衍生物，存在于多种人类饮食成分中，在生物系统中具有重要且广泛的作用，包括抗癌、抗炎、抗氧化、心脏保护、抗老化作用以及对代谢疾病的有益特性。本研究探讨了长期给予白藜芦醇对肥胖Zucker大鼠代谢综合征实验模型所产生的几种功能改变的影响以及其中可能涉及的机制。在接受白藜芦醇治疗的肥胖大鼠中，肥胖Zucker大鼠体内发现的高血浆甘油三酯、总胆固醇、游离脂肪酸、胰岛素和瘦素浓度有所降低。此外，用白藜芦醇治疗的肥胖大鼠肝脏脂质含量显著降低，这一效应与这些动物肝脏中5'-AMP激活蛋白激酶（AMPK）和乙酰辅酶A羧化酶（ACC）磷酸化增加有关。白藜芦醇治疗还改善了该模型特有的炎症状态，因为它增加了肥胖Zucker大鼠内脏脂肪组织（VAT）中脂联素的浓度并降低了肿瘤坏死因子-α的产生。此外，长期摄入白藜芦醇可增强肥胖Zucker大鼠VAT中的eNOS表达。这些效应与该组织中AMPK的激活和ACC的磷酸化抑制平行。在接受白藜芦醇治疗的肥胖大鼠中，肥胖Zucker大鼠升高的收缩压和降低的主动脉eNOS表达得到了显著改善。总之，白藜芦醇改善了肥胖Zucker大鼠的血脂异常、高胰岛素血症、高瘦素血症和高血压，并在VAT中产生了抗炎作用，这些作用似乎是由AMPK激活介导的。
