Vagal Oxytocin Receptors as Molecular Targets in Gut-Brain Signaling: Implications for Appetite, Satiety, Obesity, and Esophageal Motility-A Narrative Review.

Oxytocin (OT), traditionally associated with reproduction and social bonding, has emerged as a key modulator of gastrointestinal (GI) physiology and appetite regulation behavior through its actions within the gut-brain axis. Central to this regulation are vagal oxytocin receptors (VORs), which are located along vagal afferent and efferent fibers and within brainstem nuclei such as the nucleus tractus solitarius and dorsal motor nucleus of the vagus. This review presents a comprehensive synthesis of current knowledge on the anatomical distribution, molecular signaling, developmental plasticity, and functional roles of VORs in the regulation of GI motility, satiety, and energy homeostasis. We highlight how VORs integrate hormonal, microbial, and stress-related cues and interact with other neuropeptidergic systems including GLP-1, CCK, and nesfatin-1. Recent advances in spatial transcriptomics, single-nucleus RNA sequencing, chemogenetics, and optogenetics are discussed as transformative tools for mapping and manipulating VOR-expressing circuits. Particular attention is given to sex differences, translational challenges, and the limited understanding of VOR function in humans. This article proposes VORs as promising therapeutic targets in dysphagia, obesity, and functional GI disorders. We outline future research priorities, emphasizing the need for integrative, cross-species approaches to clarify VOR signaling and guide the development of targeted, personalized interventions.