Lymphatic valve dysfunction, which impairs unidirectional lymph transport, is associated with animal models of obesity, with6 or without26 ApoE deficiency, and in models of TNFα hyperactivity.18,27 Lymphatic collecting vessel hyperpermeability, which counteracts the central return of lymph, has been demonstrated in animal models of obesity5,6,26,28 and in a model of type 2 diabetes.29 However, the mechanisms by which lymphatic dysfunction contributes to or results from the primary disease are not clear. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.