Exercise-induced changes in renal URAT1 activity and expression in rats

During exercise, the plasma urate levels and urinary excretion increase due to the enhanced purine degradation in skeletal muscle. Although urate transporter-1 (URAT1) is the main transporter responsible for the reabsorption of filtered urate, potential changes in its activity and expression during exercise have not been studied yet. Therefore, the effect of heavy muscle activity on renal URAT1 activity and expression was investigated in this study. Wistar rats were used in the study and the experimental design consisted of three groups: a control group, an exercise group where animals were exhausted once a day for 5 days, and a hyperuricemia group, which was induced by an uricase inhibitor, oxonic acid. URAT1 activity measurements were performed in isolated proximal tubule segments and expression of URAT1 mRNA and protein levels were determined by the reverse transcription polymerase chain reaction and western blot analyses, respectively. Increased citrate synthase activity in soleus muscle of exercised animals proved the efficiency of our exercise protocol. Proteinuria, glucosuria, and hypoglycemia were observed only in exercised animals; however, plasma and urinary urate levels were found to be elevated in both exercising and hyperuricemia groups. Moreover, in both of the groups URAT1 transporter activity was found to be increased despite the significant decrease in URAT1 protein levels. Considering the similar changes of urate metabolism observed in both exercising and hyperuricemic rats, our results suggest that exercise-induced changes in URAT1 expression and activity depend on the increased urate concentration in plasma.