Recent studies including our own demonstrated that the cfDNA-TLR9 pathway plays a pivotal role in the pathogenesis of adipose tissue inflammation and vascular inflammation via pro-inflammatory activation of macrophages, leading to the development of cardiometabolic disorders including obesity-related insulin resistance and atherosclerosis (Fig. 5). This evidence concerns the gene TLR9 and obesity due to melanocortin 4 receptor deficiency.