METABOLIC AND ANTIOXIDANT EFFECTS OF URIC ACID IN OBESITY

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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.