Role of Uric Acid in Cardiovascular and Renal Disease

描述（由申请人提供）：尿酸在心血管和肾脏疾病中的作用我们目前有肥胖症的流行，三分之二的美国人口超重或坦率地说肥胖。27%的人患有代谢综合征，这是一种已知的糖尿病前期疾病，7%的人患有糖尿病。至关重要的是，我们必须确定可能的机制来解释这一重大流行病。虽然毫无疑问有多种原因，包括过多的热量摄入和缺乏运动，但我们已经确定了另一种可能的机制。具体来说，存在于某些甜味剂和糖中的果糖可以在大鼠中迅速引起代谢综合征，并且在流行病学上也与肥胖的增加有关。果糖与其他糖类不同，它能迅速提高血液中的尿酸水平。在之前的RO-1中，我们发现尿酸对血压、血管疾病、肾脏疾病和炎症有多重影响，特别是我们发现尿酸可以减少血管细胞的一氧化氮释放。我们已经进一步证明，果糖通过增加尿酸的方式，会导致大鼠肥胖、胰岛素抵抗和脂质异常，而这可以通过降低尿酸来部分预防。在本应用中，我们将进一步研究尿酸导致该综合征的机制，并剖析果糖如何激活导致肥胖和代谢综合征的这一途径。研究将包括确定果糖的关键特征，这些特征是诱发该综合征所必需的，重点是果糖的类型及其在高血压中的作用。我们还将研究继发于果糖的尿酸的升高是如何引起该综合征的特征的，重点是果糖和尿酸是如何扰乱正常的血管系统的，将其从一个非炎症和扩张的系统转变为一个炎症和收缩的系统。最后，我们将探讨果糖和尿酸可能对脂肪细胞有直接影响的可能性。了解尿酸和果糖引起代谢综合征的途径，可能会为肥胖症流行的发病机制及其对心血管和肾脏疾病的影响提供新的见解。

DESCRIPTION (provided by applicant): Role of Uric Acid in Cardiovascular and Renal Disease We are currently having an epidemic of obesity, with two-thirds of the US population either overweight or frankly obese. Twenty-seven percent of our population have the metabolic syndrome, a known prediabetic condition, and 7% have diabetes. It is critical that we identify potential mechanisms to account for this great epidemic. While there are no doubt multiple causes, including excessive caloric intake and physical inactivity, we have identified another possible mechanism. Specifically, fructose, present in certain sweeteners and sugar, can rapidly induce metabolic syndrome in rats and has also been epidemiologically linked with the rise in obesity. Fructose is unlike all other sugars in that it raises uric acid rapidly in the blood. During the previous RO-1 we have found that uric acid has multiple effects on blood pressure, vascular disease, kidney disease and inflammation, and in particular we have found that uric acid can reduce nitric oxide release from vascular cells. We have further shown that fructose, by way of increasing uric acid, can cause obesity, insulin resistance and lipid abnormalities in rats, and that this can be partially prevented by lowering uric acid. In this application we will further investigate the mechanism by which uric acid contributes to this syndrome, and also dissect how fructose activates this pathway that leads to obesity and the metabolic syndrome. Studies will include determining the critical features about fructose that are necessary to induce the syndrome, with an emphasis on the type of fructose and its role in hypertension. We will also investigate how the rise in uric acid secondary to fructose causes features of the syndrome, with an emphasis on how fructose and uric acid disturb the normal vasculature, converting it from a noninflamed and dilated system to one that is inflamed and constricted. Finally, we will explore the possibility that fructose and uric acid may have direct effects on fat cells. Understanding the pathways by which uric acid, and fructose, can cause metabolic syndrome may give new insights into the pathogenesis of the obesity epidemic, with its impact on cardiovascular and kidney disease. Project Narrative: This study looks at the role of uric acid and fructose in the development of metabolic syndrome. The role of these factors in this syndrome, have not been widely studied. Identifying a casual role for these factors could lead to new treatments for metabolic syndrome.