Uric acid in metabolic syndrome: From an innocent bystander to a central player

Abstract

Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases.

Keywords: Cardiovascular disease; Diabetes mellitus; Hypertension; Kidney disease; Metabolic syndrome; Uric acid.

Fig. 1

Uric acid induced effects that may play a role in the pathogenesis of hypertension, diabetes, and obesity.

Fig. 2

Relationship between high-fructose diet, generation of hyperuricemia and resulting metabolic syndrome. Renal disease is linked to both metabolic syndrome and hyperuricemia in a mutual way.

Fig. 3

Schematic diagram showing complex interaction of uric acid, components of metabolic syndrome and cardiovascular disease. Note that elevated uric acid can lead to development of individual components and these components in turn can lead to elevations in serum uric acid. Elevated serum and intracellular uric acid may lead to increased incidence of cardiovascular disease both directly through inflammation, oxidative stress and endothelial dysfunction and indirectly through developing other established cardiovascular risk factors such as hypertension, diabetes and visceral obesity.