Abstract
Fructose consumption has been recently related to an epidemic of metabolic syndrome, and hyperuricemia plays a pathogenic role in fructose-induced metabolic syndrome. Fructose-fed rats showed hyperuricemia and renal dysfunction with reductions of the urinary uric acid/creatinine ratio and fractional excretion of uric acid (FE(ur)), as well as other features of metabolic syndrome. Lowering serum uric acid levels with allopurinol, rutin, and quercetin increased the urinary uric acid/creatinine ratio and FE(ur) and attenuated other fructose-induced metabolic abnormalities in rats, demonstrating that hyperuricemia contributed to the deficiency of renal uric acid excretion in this model. Furthermore, we found that fructose upregulated the expression levels of rSLC2A9v2 and renal-specific transporter (rRST), downregulated the expression levels of organic anion transporters (rOAT1 and rUAT) and organic cation transporters (rOCT1 and rOCT2), with the regulators prostaglandin E(2) (PGE(2)) elevation and nitric oxide (NO) reduction in rat kidney. Allopurinol, rutin, and quercetin reversed dysregulations of these transporters with PGE(2) reduction and NO elevation in the kidney of fructose-fed rats. These results suggested that dysregulations of renal rSLC2A9v2, rRST, rOAT1, rUAT, rOCT1, and rOCT2 contributed to fructose-induced hyperuricemia and renal dysfunction. Therefore, these renal transporters may represent novel therapeutic targets for the treatment of hyperuricemia and renal dysfunction in fructose-induced metabolic syndrome.
Full text
