Rivera Leonor, Morón Rocío, Sánchez Manuel, Zarzuelo Antonio, Galisteo Milagros
Department of Pharmacology, CIBER-EHD, School of Pharmacy, University of Granada, Granada, Spain.
Obesity (Silver Spring). 2008 Sep;16(9):2081-7. doi: 10.1038/oby.2008.315.
The aim of this study was to analyze the effects of chronic administration of high doses of quercetin on metabolic syndrome abnormalities, including obesity, dyslipidemia, hypertension, and insulin resistance. For this purpose, obese Zucker rats and their lean littermates were used. The rats received a daily dose of quercetin (2 or 10 mg/kg of body weight) or vehicle for 10 weeks. Body weight and systolic blood pressure (SBP) were recorded weekly. At the end of the treatment, plasma concentrations of triglycerides, total cholesterol, free-fatty acids (FFAs), glucose, insulin, adiponectin, and nitrate plus nitrite (NOx) were determined. Tumor necrosis factor-alpha (TNF-alpha) production, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) protein expression were analyzed in visceral adipose tissue (VAT). The raised SBP and high plasma concentrations of triglycerides, total cholesterol, FFA, and insulin found in obese Zucker rats were reduced in obese rats that received either of the doses of quercetin assayed. The higher dose also improved the inflammatory status peculiar to this model, as it increased the plasma concentration of adiponectin, reduced NOx levels in plasma, and lowered VAT TNF-alpha production in obese Zucker rats. Furthermore, chronic intake of the higher dose of quercetin enhanced VAT eNOS expression among obese Zucker rats, whereas it downregulated VAT iNOS expression. In conclusion, both doses of quercetin improved dyslipidemia, hypertension, and hyperinsulinemia in obese Zucker rats, but only the high dose produced antiinflammatory effects in VAT together with a reduction in body weight gain.
本研究的目的是分析长期高剂量给予槲皮素对代谢综合征异常情况的影响,这些异常包括肥胖、血脂异常、高血压和胰岛素抵抗。为此,使用了肥胖的 Zucker 大鼠及其瘦的同窝仔鼠。大鼠连续 10 周每日接受一剂槲皮素(2 或 10 mg/kg 体重)或赋形剂。每周记录体重和收缩压(SBP)。在治疗结束时,测定血浆甘油三酯、总胆固醇、游离脂肪酸(FFA)、葡萄糖、胰岛素、脂联素以及硝酸盐加亚硝酸盐(NOx)的浓度。分析内脏脂肪组织(VAT)中肿瘤坏死因子-α(TNF-α)的产生、诱导型一氧化氮合酶(iNOS)和内皮型一氧化氮合酶(eNOS)的蛋白表达。在接受任一剂量槲皮素测定的肥胖大鼠中,肥胖 Zucker 大鼠中升高的 SBP 以及甘油三酯、总胆固醇、FFA 和胰岛素的高血浆浓度均有所降低。较高剂量还改善了该模型特有的炎症状态,因为它增加了肥胖 Zucker 大鼠血浆脂联素的浓度,降低了血浆中 NOx 的水平,并降低了 VAT 中 TNF-α 的产生。此外,长期摄入较高剂量的槲皮素可增强肥胖 Zucker 大鼠 VAT 中 eNOS 的表达,而它下调了 VAT 中 iNOS 的表达。总之,两种剂量的槲皮素均改善了肥胖 Zucker 大鼠的血脂异常、高血压和高胰岛素血症,但只有高剂量在 VAT 中产生抗炎作用并减少体重增加。