Acupuncture ameliorates diet-induced obesity via the vagal–GLP-1–ARC circuit: neural mechanism of anorexigenic action

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