Resveratrol affects the expression of uric acid transporter by improving inflammation

Resveratrol (RSV), a polyphenol, non-flavonoid plant-derived antitoxin, ameliorates hyperuricemia and kidney inflammation. The present study aimed to establish a model of high-fat diet (HFD)-induced insulin resistance (IR) and to determine the specific mechanism of RSV to improve kidney inflammation and reduce uric acid (UA). C57BL/6J mice were fed a HFD for 12 weeks and their glucose tolerance was evaluated by intraperitoneal glucose tolerance testing. The mice were then administered RSV for 6 weeks, and blood and kidney samples were collected. Serum UA and insulin concentrations were determined using ELISA kits. Hematoxylin and eosin, periodic acid-Schiff and Masson staining were performed to observe the pathological changes of the kidney, and electron microscopy was used to observe changes in the kidney ultrastructure. The renal concentrations of interleukin (IL)-6, IL-18, IL-1β and tumor necrosis factor-α (TNF-α) were measured using ELISA kits, and western blotting evaluated changes in the protein expression levels of various indicators. RSV significantly ameliorated HFD-induced IR and reduced blood UA levels. Long-term IR can lead to lipid deposition, glycogen accumulation, inflammatory damage and fibrotic changes in the kidney of mice. This leads to a significant increase in the expression of UA transport-related proteins, an increase in UA reabsorption and an increase in blood UA levels. Notably, RSV intervention was able to reverse this process. The effect of RSV may be achieved by inhibiting the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88/nuclear factor-κB signaling pathway. In conclusion, RSV may improve kidney inflammation through TLR4 and NLRP3 signaling pathways, and reduce the expression of UA transporter proteins in the kidney of insulin-resistant mice, thereby reducing blood UA levels.