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.
Cao et al. (Thu,) studied this question.