MAP4K4 and obesity due to melanocortin 4 receptor deficiency: In contrast, the function of an EC-derive mitogen activated protein kinase kinase kinase kinase 4 (MAP4K4) has opposing functions in blood and lymphatic ECs: while MAP4K4 is required for lymphatic vascular integrity, blood EC-MAP4K4 induces insulin resistance by impairing vascular function in obesity (90).