Being aware of the fact that reduced BDNF and NGF serum and tissue levels have been associated with hyperinsulinemic states like obesity and type-2-diabetes (Molteni et al., 2002; Geroldi et al., 2006; Suwa et al., 2006; Bullo et al., 2007; Krabbe et al., 2007; Fujinami et al., 2008; Yamanaka et al., 2008; Golden et al., 2010), even a causal relationship between overactive insulin signaling and decreased neurotrophin levels as part of a negative feedback mechanism is imaginable (Ding et al., 2006). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.