The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis

The pathogenesis of gouty arthritis (GA) begins with the deposition of monosodium urate (MSU) crystals in the joints. This crystal deposition triggers a critical inflammatory response by activating the NLRP3 inflammasome, which in turn drives the maturation and release of pro-inflammatory cytokines such as IL-1β. Beyond this well-defined inflammatory axis, metabolic dysregulation is increasingly recognized as a core component of GA pathogenesis. This paper systematically reviews the crosstalk between metabolic signaling and the NLRP3 inflammasome in GA, elucidating how MSU crystals serve as a bridge between hyperuricemia (HUA) and innate immune activation. Furthermore, we elaborate the dual role of metabolic factors: acting both as "primer" and "amplifiers" of NLRP3 inflammasome activation, significantly lowering its activation threshold. This mechanistic association offers novel therapeutic insights for GA management: synergistic regulation of metabolic signaling alongside targeted inhibition of NLRP3 inflammasome activation enables more effective therapeutic interventions. Defining gout as a "metabolic-inflammatory" disorder has led to the development of novel dual-target therapeutic strategies-simultaneously alleviating inflammatory symptoms while regulating metabolic abnormalities. Such approaches hold significant promise for effectively preventing and controlling gout attacks, whilst reducing the risk of long-term complications.