Central nervous system appetite-regulating targets (CNS-ART)

Central nervous system (CNS) appetite-regulating targets comprise a complex network of receptors and neuropeptides primarily located in the hypothalamus and brainstem that integrate metabolic, hedonic, and environmental signals to maintain energy homeostasis [5, 8]. Key nodes in this system include the arcuate nucleus (ARC), which contains orexigenic NPY/AgRP neurons and anorexigenic POMC/CART neurons, and the paraventricular nucleus (PVN), which expresses the melanocortin 4 receptor (MC4R) [6, 9]. These targets respond to peripheral hormones such as leptin, insulin, and ghrelin, as well as gut-derived peptides like GLP-1 and PYY [7, 8]. Dysregulation of these pathways is a central feature of obesity and related metabolic disorders, making them prime candidates for pharmacological intervention [1, 4]. Current therapeutic strategies involve the use of GLP-1 receptor agonists (e.g., semaglutide) and MC4R agonists (e.g., setmelanotide) to promote weight loss by enhancing satiety and reducing caloric intake [5, 7]. However, targeting the CNS for appetite control presents significant challenges, including the risk of psychiatric side effects and the need for high specificity to avoid off-target autonomic or cardiovascular complications [5, 9].

Other names

Appetite-regulating receptorsHypothalamic feeding targetsCNS satiety centersFeeding behavior regulators

Modulation of hypothalamic and brainstem signaling pathways through agonism or antagonism of specific receptors (e.g., MC4R, GLP-1R, 5-HT2CR) to enhance satiety or suppress hunger signals.