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. Fructose intake either as sucrose or High fructose corn syrup has been recently linked with the epidemic of obesity and metabolic syndrome. We have identified a potential pathway by which fructose may cause this syndrome. Specifically, fructose intake results in the rapid increase in serum uric acid over 30- 60 minutes. In turn, we have found that uric acid can inhibit endothelial nitric oxide bioavailability. Blocking NO has been found to be a mechanism for insulin resistance, since insulin stimulates glucose uptake in skeletal muscle in part by increasing blood flow via an NO dependent mechanism. Consistent with this hypothesis, we have found that we can prevent or reverse many features of the metabolic syndrome in rats by lowering their uric acid with allopurinol.