Lin Jie, Shen Yikai, Xia Yiwen, Li Ying, Jiang Tianlu, Shen Xusheng, Fu Yiwang, Zhang Diancai, Yang Li, Xu Hao, Xu Zekuan, Wang Linjun
Gastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Hepatobiliary Surgery, Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Mol Cell Endocrinol. 2025 Apr 1;599:112464. doi: 10.1016/j.mce.2025.112464. Epub 2025 Jan 21.
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.
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.
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.
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.
肠-脑轴（GBA）参与多种生理活动的调节，迷走神经在此过程中起重要作用。然而，迷走神经功能与营养调节之间的关联仍不清楚。在此，我们探究了迷走神经切断术后小鼠营养状况的变化，并研究了导致这些变化的潜在机制。
我们对小鼠进行了迷走神经切断术，并使用免疫荧光染色验证神经切断情况。然后我们观察了小鼠的食物摄入量和体重，并使用酶联免疫吸附测定（ELISA）试剂盒检测营养和炎症相关标志物。使用qRT-PCR和ELISA试剂盒确定胰高血糖素样肽1（GLP-1）在GBA中的作用。使用蛋白质免疫印迹法和ELISA试剂盒探究潜在机制。
迷走神经切断术后，小鼠的营养状况恶化，表现为体重和食物摄入量显著降低。编码GLP-1的胰高血糖素原基因（GCG）的表达在迷走神经切断术后显著增加。机制上，乙酰胆碱（ACh）逆转了高糖（HG）诱导的GLP-1分泌升高。ACh上调了AMPKα磷酸化，从而减少GLP-1分泌。此外，ACh通过M3AChR增强了AMPKα磷酸化水平。
在正常生理条件下，迷走神经释放的ACh抵消了GLP-1的厌食作用。迷走神经切断术阻断了这种反馈，导致小鼠食物摄入量和体重下降。
