Since targeted deletion of eNOS increases susceptibility to diet-induced obesity (Nakata et al., 2008) and mice with targeted deletion of iNOS on high-fat diet gain weight analogous to WT mice but without an increase in insulin resistance (Perreault and Marette, 2001), this suggests that the loss of nNOS may be protective against diet-induced obesity. Here, NOS1 is linked to obesity due to melanocortin 4 receptor deficiency.