2. Academic Validation
  3. Vagotomy suppresses food intake by increasing GLP-1 secretion via the M3 AChR-AMPKα pathway in mice

Vagotomy suppresses food intake by increasing GLP-1 secretion via the M3 AChR-AMPKα pathway in mice

  • Mol Cell Endocrinol. 2025 Apr 1:599:112464. doi: 10.1016/j.mce.2025.112464.
Jie Lin 1,  Yikai Shen 1,  Yiwen Xia 1,  Ying Li 2,  Tianlu Jiang 3,  Xusheng Shen 1,  Yiwang Fu 1,  Diancai Zhang 1,  Li Yang 1,  Hao Xu 1,  Zekuan Xu 4,  Linjun Wang 5
Affiliations

Affiliations

  • 1 Gastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • 2 Hepatobiliary Surgery, Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • 3 Department of General Surgery, Wuxi Medical Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi Peolple's Hospital, Wuxi, Jiangsu Province, China.
  • 4 Gastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China. Electronic address: xuzekuan@njmu.edu.cn.
  • 5 Gastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. Electronic address: wanglinjun@njmu.edu.cn.
PMID: 39848433 DOI: 10.1016/j.mce.2025.112464
Abstract

Objective: The gut-brain axis (GBA) is involved in the modulation of multiple physiological activities, and the vagus nerve plays an important role in this process. However, the association between vagus nerve function and nutritional regulation remains unclear. Here, we explored changes in the nutritional status of mice after vagotomy and investigated the underlying mechanisms responsible for these changes.

Methods: We performed vagotomies in mice and verified nerve resection using immunofluorescence staining. We then observed the food intake and body weight of the mice and tested nutritional and inflammation-related markers using enzyme-linked immunosorbent assay (ELISA) kits. The role of glucagon-like peptide 1 (GLP-1) in the GBA was determined using qRT-PCR and ELISA kits. Western blot and ELISA kits were used to explore the underlying mechanisms.

Results: After vagotomy, the mice experienced a deterioration in their nutritional status, which manifested as a significant reduction in body weight and food intake. The expression of the proglucagon gene (GCG), which encodes GLP-1, significantly increased after vagotomy. Mechanistically, acetylcholine (ACh) reversed the HG (high glucose) -induced elevation of GLP-1 secretion. ACh upregulated AMPKα phosphorylation, thereby reducing GLP-1 secretion. Moreover, the level of AMPKα phosphorylation was enhanced by ACh via M3AChR.

Conclusions: ACh released by the vagus nerve counteracts the anorectic effects of GLP-1 under normal physiological conditions. Vagotomy blocks this feedback, resulting in a loss of food intake and body weight in mice.

Keywords

ACh; AMPKα; Food intake; GLP-1; Vagotomy.

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