Apelin-13 reduces oxidative stress induced by uric acid via downregulation of renin-angiotensin system in adipose tissue

Abstract Apelin-13, a novel adipocytokine, is found to be a powerful antioxidant. Our previous work reported that uric acid could induce oxidative stress via an activation of renin–angiotensin system (RAS) in 3T3-L1 adipocytes. In the present study, we tried to observe the effect of apelin-13 on uric acid-induced oxidative stress. We also tried to reveal the potential mechanisms. In vivo, the rats were fed with 60% fructose diet for 8 weeks to produce hyperuricemia. Then, the hyperuricemia rats were intraperitoneally injected with apelin-13 for 2 weeks or 12 weeks. In vitro, 3T3-L1 adipocytes were treated with apelin-13 in the presence of 600 μmol/L uric acid for 48 h. When injected with apelin-13 for 12 weeks, the hyperuricemia rats had ameliorated oxidative stress, downregulated RAS components and upregulated angiotensin type 1 receptor related protein (APJ) expression in adipose tissue. Serum uric acid levels were also decreased after treatment. However, 2-week apelin-13 treatment had no obvious effect on the rats with hyperuricemia. Consistent with the findings in vivo, in vitro study, apelin-13 could ameliorate oxidative stress, decrease tissue RAS components, and increase APJ expression in 3T3-L1 adipocytes stimulated by uric acid. In conclusion, apelin-13 reduces uric acid-induced oxidative stress in adipose tissue, maybe through the inhibition of adipose RAS expression.