In our study, long-term low-dose administration of BAM15, a mitochondrial protonophore with more specific action on MMP and less toxicity (55), confers protection against obesity-induced vascular inflammation and atherosclerosis by blocking the mtSuperoxide/NLRP3 inflammasome/caspase-1/IL-1β signaling axis, independent of body weight and lipid profiles. The gene discussed is CASP1; the disease is obesity due to melanocortin 4 receptor deficiency.