title: Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome.
abstract: 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.
authors.affiliation: Division of Nephrology, Hypertension, and Transplantation, University of Florida, Gainesville, FL 32610, USA. nakagt@medicine.ufl.edu
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Tuttle
authors.forename: Robert A
authors.initials: RA
authors.lastname: Short
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D005632:Fructose / Q000009:adverse effects*; D006801:Humans; D033461:Hyperuricemia / Q000139:chemically induced* / Q000150:complications*; D024821:Metabolic Syndrome / Q000453:epidemiology* / Q000209:etiology*; D009765:Obesity / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D005632:Fructose