Nakagawa Takahiko, Tuttle Katherine R, Short Robert A, Johnson Richard J
Division of Nephrology, Hypertension, and Transplantation, University of Florida, Gainesville, FL 32610, USA.
Nat Clin Pract Nephrol. 2005 Dec;1(2):80-6. doi: 10.1038/ncpneph0019.
The increasing incidence of obesity and the metabolic syndrome over the past two decades has coincided with a marked increase in total fructose intake. Fructose--unlike other sugars--causes serum uric acid levels to rise rapidly. We recently reported that uric acid reduces levels of endothelial nitric oxide (NO), a key mediator of insulin action. NO increases blood flow to skeletal muscle and enhances glucose uptake. Animals deficient in endothelial NO develop insulin resistance and other features of the metabolic syndrome. As such, we propose that the epidemic of the metabolic syndrome is due in part to fructose-induced hyperuricemia that reduces endothelial NO levels and induces insulin resistance. Consistent with this hypothesis is the observation that changes in mean uric acid levels correlate with the increasing prevalence of metabolic syndrome in the US and developing countries. In addition, we observed that a serum uric acid level above 5.5 mg/dl independently predicted the development of hyperinsulinemia at both 6 and 12 months in nondiabetic patients with first-time myocardial infarction. Fructose-induced hyperuricemia results in endothelial dysfunction and insulin resistance, and might be a novel causal mechanism of the metabolic syndrome. Studies in humans should be performed to address whether lowering uric acid levels will help to prevent this condition.
在过去二十年中，肥胖症和代谢综合征的发病率不断上升，与此同时，果糖的总摄入量显著增加。与其他糖类不同，果糖会使血清尿酸水平迅速升高。我们最近报告称，尿酸会降低内皮一氧化氮（NO）的水平，而内皮一氧化氮是胰岛素作用的关键介质。一氧化氮可增加流向骨骼肌的血流量并增强葡萄糖摄取。缺乏内皮一氧化氮的动物会出现胰岛素抵抗和代谢综合征的其他特征。因此，我们认为代谢综合征的流行部分归因于果糖诱导的高尿酸血症，它会降低内皮一氧化氮水平并诱发胰岛素抵抗。与这一假设相符的是，在美国和发展中国家，平均尿酸水平的变化与代谢综合征患病率的上升相关。此外，我们观察到，在首次发生心肌梗死的非糖尿病患者中，血清尿酸水平高于5.5mg/dl可独立预测6个月和12个月时高胰岛素血症的发生。果糖诱导的高尿酸血症会导致内皮功能障碍和胰岛素抵抗，可能是代谢综合征的一种新的致病机制。应开展人体研究以探讨降低尿酸水平是否有助于预防这种疾病。
