Vagus nerve stimulation for obesity: an electrical-targeting perspective on physiological themes and translational challenges

Abstract Implantable vagus nerve stimulation (VNS) has been explored as a programmable bioelectronic approach for modulating feeding and metabolic function in obesity. However, obesity-related VNS is not a single uniform intervention. Studies differ in stimulation site, electrode interface, waveform, stimulation schedule, stimulation mode, animal model, and physiological readout, making interpretation difficult. This review examines implantable obesity-related VNS from an electrical-targeting perspective. We summarize stimulation-relevant vagal physiology and map major electrical strategies, including cervical VNS, abdominal and subdiaphragmatic activating VNS, high-frequency vagal blockade, and emerging responsive or self-powered interfaces. Reported outcomes are interpreted in relation to satiation, reward-related feeding, glucose handling, nutrient metabolism, energy expenditure, inflammatory regulation, and obesity-associated changes in vagal signaling. Overall, obesity-oriented VNS should be understood as a family of electrical interventions applied to a complex vagal system, rather than as a single therapeutic modality.