Obesity triggers NLRP3 inflammasome hyperactivation by rewiring nucleotide metabolism. In macrophages, obesity impairs SAMHD1 function, causing dNTP accumulation. This drives mtDNA neosynthesis and the release of oxidized fragments, fueling chronic inflammation and insulin resistance.

References:

• Liu D, Zhou C, Wang X, et al. Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity[J]. Science, 2026, 391(6782): eadq9006.