Uric acid and Metabolic Syndrome: What is the Relationship?

Miguel      A. Lanaspa; Yuri      Y. Sautin; A.      Ahsan Ejaz; Magdalena      Madero; MyPhuong      Le; Jacek      Manitius; Laura      Gabriela Sanchez-Lozada; Takahiko      Nakagawa; Richard      J. Johnson

doi:10.2174/157339711795305004

Abstract

An elevated uric acid is common in subjects with insulin resistance and obesity, and is in effect part of the metabolic syndrome complex. In this paper we review evidence for a potential causal role of uric acid in the metabolic syndrome. While some studies suggest that uric acid may simply be a consequence of the presence of oxidative stress or hyperinsulinemia present in subjects with metabolic syndrome, there is increasing evidence that uric acid could have a contributory causal role. First, an elevated serum uric acid often precedes the development of obesity and metabolic syndrome. Second, experimental and clinical studies provide increasing evidence that excessive intake of fructose, primarily in the form of added sugars, may have a key role in the development of metabolic syndrome. Fructose increases uric acid levels, and lowering uric acid in fructose fed rats can improve insulin resistance and features of metabolic syndrome. The mechanism may be via the improvement in endothelial function and due to direct actions of uric acid on adipocytes. However, the lowering of uric acid in human subjects ingesting high doses of fructose was associated with improvement in blood pressure but not in other features of metabolic syndrome. Clearly more studies are needed to better understand the role of uric acid in metabolic syndrome, but it seems likely that uric acid may have a role as both a marker and potential modifier of the metabolic syndrome.

Keywords: Uric acid, metabolic syndrome, fructose, insulin resistance, hyperuricemia, SLC2A9, uricosuria, allopurinol, hyperlipidemia, hyperinsulinemia