Recent reports of small molecule NNMT inhibitors, which increase cellular NAD+ levels leading to metabolic benefits such as the reversal of diet-induced obesity and prevention of muscle senescence (Neelakantan et al, 2019; Neelakantan et al, 2018; Sampson et al, 2021) supports the viability of modulating NNMT activity to achieve these goals. Here, NNMT is linked to obesity due to melanocortin 4 receptor deficiency.