METABOLIC AND ANTIOXIDANT EFFECTS OF URIC ACID IN OBESITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肥胖与胰岛素抵抗、非感染性全身炎症、心血管功能障碍和高尿酸血症有关。尽管血清尿酸(UA)的显著增加增加了肾结石和痛风性关节炎的风险，但UA的增加可能会对临床产生有益的影响，因为UA是一种主要的内源性血浆抗氧化剂。增强抗氧化能力可能会阻止参与炎症、胰岛素抵抗和心血管疾病发病机制的氧化途径。这项研究的总体目标是评估肥胖受试者血清UA浓度增加可减少氧化应激、降低血浆炎症标志物、改善内皮功能和提高胰岛素敏感性的假说。这一假设将通过(1)比较血浆UA浓度高或正常的肥胖者的胰岛素敏感性、内皮功能、炎症标记物、氧化应激和血浆总抗氧化能力，以及(2)确定别嘌醇治疗降低血浆UA浓度对肥胖症高尿酸血症患者的氧化状态、炎症标志物、内皮功能和代谢异常的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is associated with insulin resistance, non-infectious systemic inflammation, cardiovascular dysfunction and hyperuricemia. Although marked increases in serum uric acid (UA) increases the risk of kidney stones and gouty arthritis, increased UA could have beneficial clinical effects, because UA is a major endogenous plasma antioxidant. Increased antioxidant capacity might prevent oxidative pathways involved in the pathogenesis of inflammation, insulin resistance, and cardiovascular disease. The overall goal of this study is to evaluate the hypothesis that increased serum UA concentration in obese subjects reduces oxidative stress, decreases plasma markers of inflammation, improves endothelial function, and increased insulin sensitivity. This hypothesis will be tested by (1) comparing insulin sensitivity, endothelial function, plasma markers of inflammation, oxidative stress, and plasma total antioxidant capacity in obese subjects with high or normal plasma UA concentrations, and by (2) determining the effects of decreasing plasma UA concentrations with allopurinol therapy on oxidative status, inflammatory markers, endothelial function, and metabolic abnormalities in obese patients with hyperuricemia.