Yanan Yang, Yuwei Shao, Jun Tian, Yuezhu Wang, Ye Zhu, Siying Pan, Xiali Wei, Linyan Jiang, Xiaoke Wang, Qing Shu
Abstract Background Electroacupuncture (EA) has demonstrated efficacy in ameliorating obesity through its marked appetite-suppressing effects. This study aims to elucidate the peripheral-central communication mechanism underlying EA's appetite inhibition mediated by the “vagal afferent fiber–nucleus tractus solitarius (NTS)–hypothalamic arcuate nucleus (ARC)” neural circuit. Methods High-fat diet-induced obese rats received EA or transcutaneous auricular vagus nerve stimulation (taVNS) for 8 weeks. Furthermore, we employed chemogenetic approaches to activate NTS glucagon-like peptide-1 (GLP-1) neurons (NTS GLP−1 ) and utilized capsaicin for gastric vagal deafferentation (GVND). Outcomes included metabolic profiles, vagal electrophysiology, expression of NTS GLP−1 and hypothalamic appetite-regulating neuropeptides, and neuronal activation markers. Results We observed reduced expression of GLP-1 in the NTS of obese rats. Chemogenetic activation of NTS GLP−1 significantly suppressed appetite, mitigated obesity, and modulated hypothalamic pro-opiomelanocortin (POMC) and neuropeptide Y (NPY). Following EA intervention in obese rats, concurrent activation of NTS GLP−1 and vagal afferent fibers was observed. Similar to chemogenetic NTS GLP−1 activation, EA upregulated the anorexigenic peptide POMC while downregulating the orexigenic peptide NPY in the ARC. Chemogenetic inhibition of GLP-1 neurons during EA application partially inhibited its anti-obesity and anorectic effects. Further investigations revealed that both EA and taVNS effectively reduced food intake and alleviated obesity. While both interventions activated vagal pathways and NTS GLP−1 , EA induced a significantly stronger activation of vagal afferent fibers compared to taVNS. Critically, GVND prior to EA application attenuated its anti-obesity effects. Conclusion The therapeutic benefits of EA in appetite suppression and obesity mitigation are mediated by selective regulation of the “vagal–GLP-1–ARC” neural circuit. Graphical Abstracts