Furthermore, systemic blockade of VEGFR-3 was demonstrated to reduce the infiltration of macrophages in adipose tissue and lipid accumulation in liver, and improve insulin sensitivity, revealing the unexpected effect of blocking VEGF-C and VEGF-D on the treatment of metabolic syndrome, which constituted a new therapeutic strategy for the prevention of obesity related insulin resistance (123). This evidence concerns the gene VEGFD and obesity due to melanocortin 4 receptor deficiency.