Nucleotide metabolism reprogramming in obesity-associated cardiovascular inflammation: a new perspective

Obesity drives cardiovascular disease primarily through chronic meta-inflammation, yet the precise molecular convergence linking nutrient excess to sustained NLRP3 inflammasome activation in macrophages has remained unclear. Obesity induces inhibitory phosphorylation of SAMHD1, resulting in cytosolic dNTP accumulation, mitochondrial import through SLC25 transporters, uncontrolled mtDNA synthesis and oxidation, and consequent NLRP3 hyperactivation. This SAMHD1–dNTP–mtDNA–NLRP3 axis is supported b