Dietary 1,3-diacylglycerol ameliorates hyperuricemia via dual modulation of urate transporters and inflammasomes in mice

Abstract

Hyperuricemia is a metabolic disorder associated with substantial health risks, whereas current clinical treatments frequently entail considerable adverse effects. This study demonstrates that dietary diacylglycerol (DAG) significantly ameliorates hyperuricemia by specifically modulating the renal urate transporter network and exerting anti-inflammatory effects. 1,3-Diacylglycerol (1,3-DAG) is metabolized into 1-monoacylglycerol in the body, which inhibits the synthesis of triglycerides. Its metabolic process differs from that of 1,2-diacylglycerol and triglycerides, exhibiting unique biological functions and metabolic pathways. The mouse model of hyperuricemia was established through the combined administration of potassium oxonate and yeast extract. Using qPCR and western blotting, we found that 1,3-DAG intervention selectively downregulated the expression of URAT1, a critical urate reabsorption transporter, while upregulating the expression of the secretory transporters OCT1 and OCT2. In addition, DAG markedly reduced serum levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, and alleviated histopathological damage in both hepatic and renal tissues. This study reveals the molecular pathways by which dietary DAG alleviates hyperuricemia and related inflammation through synergistic actions on multiple targets, thus offering a robust theoretical basis for formulating lipid-based dietary strategies against hyperuricemia.