Mouse models depleted of MRAP2 have extreme obesity, increased fat mass and visceral adiposity, analogous to MC4R knockout mice [15, 16]; while double knockouts of MRAP2 and MC4R further demonstrated that MRAP2 facilitates the action of MC4R, but that there are also MC4R-independent mechanisms [17]. This evidence concerns the gene MC4R and obesity due to melanocortin 4 receptor deficiency.