Circadian rhythm
Research into appetite-suppressants have further highlighted the role of the melanocortin system in weight homeostasis. Nicotine's appetite-suppressant effect appears to result from nicotine's stimulation of α3β4 nAChR receptors located in the POMC neurons in the arcuate nucleus and subsequently the melanocortin system via the melatocortin-4 receptors on second-order neurons in the paraventricular nucleus of the hypothalamus. Serotonin plays an essential role in mediating energy balance, including appetite suppression and weight reduction, by stimulation of the melanocortin-4 receptors, as was previously hypothesized, by a pathway to the brain stem via the hypothalamus, even though there are also peripheral pathways. Circadian rhythm signals also affect the melanocortin system, both directly with melatonin affecting POMC gene expression in the arcuate nucleas, and indirectly via the interdependence between serotonin and melatonin cycles. Selenoproteins indirectly regulate the melatocortin system via redox homeostasis.