On the other hand, the intake of rewarding substances, like sucrose or alcohol, has been shown to increase endogenous RLN-3 levels in the brain (Ryan et al., 2014); and in rats with diet-induced obesity (DIO) it was shown that central RLN-3 expression is constitutively increased, and that refeeding after food deprivation stimulates the orexigenic effect of RLN-3 through the increase of RXFP-3 expression in brain areas that regulate food intake (Lenglos et al., 2014). Here, RLN3 is linked to obesity due to melanocortin 4 receptor deficiency.