Since these effects occurred in the absence of significant differences in body weight, our data suggest that, in normal animals, PVNTH neurons play a physiological role in promoting normal glucose homeostasis — independently of the control of body weight — and that inhibition of these neurons by increased PRR signaling contributes to the effect of obesity to impair glucose homeostasis. This evidence concerns the gene ATP6AP2 and obesity due to melanocortin 4 receptor deficiency.