Transcutaneous auricular vagus nerve stimulation inhibits food intake and body weight gain through the orexin dependent pathway in high fat diet mice

Obesity represents a significant global health challenge, adversely affecting both physical and mental well-being. Neuromodulation techniques have demonstrated efficacy in promoting weight loss by regulating appetite. Recently, transcutaneous vagus nerve stimulation (taVNS) has garnered considerable attention. This study aims to investigate the effects of taVNS on food intake, body weight, and blood glucose levels in mice subjected to a high-fat diet (HFD), and to explore its potential mechanisms. Balb/c male mice were randomly assigned to three groups: control group, HFD + sham electroacupuncture group, and HFD + taVNS group (n = 10). The taVNS group received daily 30-min sessions of intermittent stimulation at 10 Hz and 1.0 mA in the bilateral cymba conchae for one week. Weight and dietary intake measurements were recorded daily at regular intervals, and fasting blood glucose levels were assessed for each group after one week of intervention. Additionally, the wet weight of adipose tissue in the epididymis, scapula, and groin was measured and recorded. Pathological changes in the liver were observed using Oil Red O and HE staining techniques. Various lipid indicators and orexin levels in mouse plasma were quantified via colorimetric and ELISA methods. To elucidate the mediating effects of brain regions on the action of taVNS, relevant neural circuits were mapped through C-fos expression, viral tracking, and chemogenetic methodologies. According to the research findings, taVNS can effectively reduce appetite and weight gain, enhance insulin sensitivity, and ultimately exert a hypoglycemic effect via the orexin-dependent neural circuit of the paraventricular nucleus-lateral hypothalamus. This suggests that taVNS is a promising treatment strategy for both obesity and diabetes.