Peptide Hormones in Appetite Regulation: A Complex Network

Background: Appetite regulation is governed by a complex neuroendocrine network that integrates peripheral peptide signals with hypothalamic and brainstem circuits to coordinate energy intake and maintain energy homeostasis. Disruption of these pathways contributes to obesity and other disorders characterised by dysregulated feeding behaviour. Objective: To map and synthesise the current evidence on the role of appetite-regulating peptide hormones and central neural pathways in appetite control, obesity pathophysiology, and emerging therapeutic approaches. Methods: A scoping review of the literature was conducted to identify and synthesise evidence relating to the physiological and pathological mechanisms of appetite regulation. The review examined the actions of key peptide hormones, including ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), leptin, and insulin, their interactions within the gut–brain axis, and their effects on central appetite-regulating circuits. Results The evidence highlights the central role of the arcuate nucleus in integrating peripheral hormonal signals with neural pathways controlling feeding behaviour. Appetite regulation is mediated by the balance between orexigenic neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons and anorexigenic pro-opiomelanocortin/cocaine- and amphetamine-regulated transcript (POMC/CART) neurons, with further modulation by the paraventricular, lateral, and ventromedial hypothalamic nuclei. The literature identifies hormone resistance, impaired satiety signalling, and altered neuroendocrine feedback as major contributors to obesity. Evidence on therapeutic interventions demonstrates the potential of GLP-1 receptor agonists, including liraglutide and semaglutide, and the dual incretin agonist tirzepatide, while also highlighting challenges related to treatment durability, adverse effects, and weight regain following discontinuation. Conclusions: Current evidence demonstrates that appetite regulation involves highly interconnected peripheral and central signalling pathways. The reviewed literature supports the development of multi-target and precision-based therapeutic strategies for obesity and identifies important areas for future research, including mechanisms of treatment resistance, long-term efficacy, and inter-individual variability in neuroendocrine responses.