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

Abstract 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 con...

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Main Authors: Yingying Zhang, Dake Song, Ruixia Liu, Hengxin Gong, Chuan Wang, Ming-gao Zhao, Kun Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-01964-6
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author Yingying Zhang
Dake Song
Ruixia Liu
Hengxin Gong
Chuan Wang
Ming-gao Zhao
Kun Zhang
author_facet Yingying Zhang
Dake Song
Ruixia Liu
Hengxin Gong
Chuan Wang
Ming-gao Zhao
Kun Zhang
author_sort Yingying Zhang
collection DOAJ
description Abstract 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.
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spelling doaj-art-a2dc7eadaacd43d1923f06fc9cf5d0792025-08-20T02:05:40ZengNature PortfolioScientific Reports2045-23222025-06-0115111210.1038/s41598-025-01964-6Transcutaneous auricular vagus nerve stimulation inhibits food intake and body weight gain through the orexin dependent pathway in high fat diet miceYingying Zhang0Dake Song1Ruixia Liu2Hengxin Gong3Chuan Wang4Ming-gao Zhao5Kun Zhang6Department of Pharmacology, School of Pharmacy, Shaanxi University of Chinese MedicineDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, Shaanxi University of Chinese MedicinePrecision Pharmacy and Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityKey Laboratory of Acupuncture and Medicine of Shaanxi Province, Shaanxi University of Chinese MedicineAbstract 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.https://doi.org/10.1038/s41598-025-01964-6Orexin-AHigh-fat dietTranscutaneous auricular vagus nerve stimulationSlimmingFood intake
spellingShingle Yingying Zhang
Dake Song
Ruixia Liu
Hengxin Gong
Chuan Wang
Ming-gao Zhao
Kun Zhang
Transcutaneous auricular vagus nerve stimulation inhibits food intake and body weight gain through the orexin dependent pathway in high fat diet mice
Scientific Reports
Orexin-A
High-fat diet
Transcutaneous auricular vagus nerve stimulation
Slimming
Food intake
title Transcutaneous auricular vagus nerve stimulation inhibits food intake and body weight gain through the orexin dependent pathway in high fat diet mice
title_full Transcutaneous auricular vagus nerve stimulation inhibits food intake and body weight gain through the orexin dependent pathway in high fat diet mice
title_fullStr Transcutaneous auricular vagus nerve stimulation inhibits food intake and body weight gain through the orexin dependent pathway in high fat diet mice
title_full_unstemmed Transcutaneous auricular vagus nerve stimulation inhibits food intake and body weight gain through the orexin dependent pathway in high fat diet mice
title_short Transcutaneous auricular vagus nerve stimulation inhibits food intake and body weight gain through the orexin dependent pathway in high fat diet mice
title_sort transcutaneous auricular vagus nerve stimulation inhibits food intake and body weight gain through the orexin dependent pathway in high fat diet mice
topic Orexin-A
High-fat diet
Transcutaneous auricular vagus nerve stimulation
Slimming
Food intake
url https://doi.org/10.1038/s41598-025-01964-6
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