Given that inflammatory stimuli suppress the production of APN,41 and that APN exhibits anti-inflammatory effects by reducing MPO release from PMN in vitro, this suggests a potential vicious cycle: inflammation in obesity reduces APN expression, leading to higher MPO release by PMN in PVAT, which in turn further reduces APN secretion and exacerbates endothelial dysfunction. This evidence concerns the gene ANPEP and obesity due to melanocortin 4 receptor deficiency.