SAMHD1 and obesity due to melanocortin 4 receptor deficiency: This SAMHD1-dNTP-mtDNA-NLRP3 axis is supported by emerging evidence as a potential upstream checkpoint that may set macrophage inflammatory tone and may contribute to three major manifestations of obesity-associated cardiovascular pathology: accelerated atherosclerosis, diastolic dysfunction in obesity cardiomyopathy, and exaggerated ischemia-reperfusion injury.