• Inhibits dermal lymphatic vessel formation and lymphangiogenesis and exhibits lymphedema phenotype in limbs• As opposed to Chy mice with a similar lack of dermal lymphatics, heterozygous K14-VEGFR-3-Ig mice did not display abnormal collagen or lipid deposition• Protected against high-fat diet-induced obesity and improved systemic insulin sensitivity by suppressing infiltration of pro-inflammatory macrophages via scavenging of VEGF-C and VEGF-D. This evidence concerns the gene VEGFC and lymphedema.