Neuroendocrine regulation of appetite

Appetite is primarily regulated by complex neuroendocrine pathways that integrate peripheral and central signals to maintain energy homeostasis. Two principal systems govern feeding behavior: the homeostatic system, which responds to metabolic needs, and the hedonic system, which is driven by reward and sensory inputs. The gastrointestinal tract, one of the largest endocrine organs, plays a pivotal role by secreting appetite-regulating hormones in response to nutrients. These signals act on central circuits, particularly within the hypothalamus, involving first-order neurons such as neuropeptide Y/agouti-related peptide and pro-opiomelanocortin/cocaine- and amphetamine-regulated transcript. In addition, gut-derived hormones like ghrelin, peptide YY, glucagon-like peptide 1, cholecystokinin, and others modulate central and vagal pathways. This review provides a detailed account of the molecular and anatomical mechanisms underlying appetite regulation, focusing on the neuroendocrine interactions between the gut and the brain.