Pharmacological inhibition of NNMT significantly shows benefits diet-induced obese mice, including reducing the body weight gain and adipocyte size, and decreasing serum cholesterol levels.642,643 These results suggest that NNMT is an appealing target for obesity and type 2 diabetes treatment.642 Together, ACMSD and NNMT provide novel targets for modulating NAD+ homeostasis, which will be of great importance to determine whether ACMSD and NNMT inhibitors can increase NAD+ levels and achieve therapeutic effects. Here, ACMSD is linked to obesity due to melanocortin 4 receptor deficiency.