GNAS and obesity due to melanocortin 4 receptor deficiency: The results from these mouse studies suggest that the effects of MC4R action in the PVN on food intake and linear growth are mediated by downstream signaling pathways that are independent of Gsα, which is further supported by studies showing that a significant proportion of human MC4R mutations associated with monogenic obesity do not show significant defects in activation of Gsα/cAMP signaling (22–24).