Finally, we turn our attention to the ever-emerging roles of nociceptin/orphanin FQ (N/OFQ) and pituitary adenylate cyclase-activating polypeptide (PACAP)—two neuropeptides that have garnered increased recognition for their regulatory impact in energy homeostasis—to further probe how the imposed regulation of energy balance circuitry by these peptides is affected by sex and altered under positive (e.g., obesity) and negative (e.g., fasting) energy balance states. The gene discussed is ADCYAP1; the disease is obesity due to melanocortin 4 receptor deficiency.