UA

Hyperuricemia is closely linked to obesity and metabolic syndrome and serves as a predictor of visceral obesity and insulin resistance. This study investigates the role of hyperuricemia in regulating key adipokines using mouse 3T3-L1 adipocytes, human primary adipocytes, and a mouse model of metabolic syndrome with hyperuricemia. Uric acid was found to increase the production of monocyte chemotactic protein-1 (MCP-1), a proinflammatory adipokine, while simultaneously suppressing adiponectin, an insulin-sensitizing and anti-inflammatory molecule. The upregulation of MCP-1 was prevented by superoxide scavenging, NADPH oxidase inhibition, or peroxisome-proliferator-activated receptor-γ (PPARγ) activation, whereas adiponectin suppression was only reversed by PPARγ stimulation. In vivo, lowering uric acid levels with allopurinol in obese mice reduced MCP-1 production, increased adiponectin levels, decreased macrophage infiltration in adipose tissue, and improved insulin resistance. These findings suggest that hyperuricemia contributes to the proinflammatory endocrine imbalance characteristic of metabolic syndrome, promoting low-grade inflammation and insulin resistance, and highlight the therapeutic potential of targeting uric acid metabolism to improve metabolic health.