In line with the potential anti-inflammatory role of IGFBP-3 in cancers and other diseases [11]–[13], [15], [16] and its crosstalk with the NF-κB pathway, our study investigates the relationship between proteolyzed IGFBP-3 in circulation and the parameters of adiposity and the potential role of IGFBP-3 in obesity-induced insulin resistance and its involvement in the progression of atherosclerosis and CVD. This evidence concerns the gene IGFBP3 and obesity due to melanocortin 4 receptor deficiency.