While stimulation of lymphangiogenesis is an attractive therapeutic target in obesity and metabolic syndrome to resolve insulin resistance, ectopic lipid deposition, and local immune cell accumulation, careful consideration is needed for the use of therapies stimulating the VEGF-C/VEGF-D/VEGFR-3 signaling axis. The gene discussed is VEGFD; the disease is obesity due to melanocortin 4 receptor deficiency.