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

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology Pub Date : 2025-01-21 DOI:10.1016/j.mce.2025.112464

Jie Lin , Yikai Shen , Yiwen Xia , Ying Li , Tianlu Jiang , Xusheng Shen , Yiwang Fu , Diancai Zhang , Li Yang , Hao Xu , Zekuan Xu , Linjun Wang

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引用次数: 0

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.

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迷走神经切断术通过增加小鼠M3 AChR-AMPKα通路GLP-1分泌来抑制食物摄入。

目的：肠脑轴（GBA）参与多种生理活动的调节，迷走神经在这一过程中起重要作用。然而，迷走神经功能与营养调节之间的关系尚不清楚。在这里，我们探讨了迷走神经切断术后小鼠营养状况的变化，并研究了这些变化的潜在机制。方法：对小鼠行迷走神经切断术，免疫荧光染色证实神经切除。然后，我们观察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。采用qRT-PCR和ELISA试剂盒检测胰高血糖素样肽1 （GLP-1）在GBA中的作用。采用Western blot和ELISA试剂盒探讨其潜在机制。结果：迷走神经切断后，小鼠的营养状况出现恶化，表现为体重和食物摄入量明显减少。编码GLP-1的胰高血糖素原基因（GCG）在迷走神经切断后表达显著升高。机制上，乙酰胆碱（ACh）逆转HG（高糖）诱导的GLP-1分泌升高。乙酰胆碱上调AMPKα磷酸化，从而减少GLP-1分泌。此外，ACh通过M3AChR增强AMPKα磷酸化水平。结论：正常生理条件下迷走神经释放乙酰胆碱可抵消GLP-1的厌食作用。迷走神经切开术阻断了这种反馈，导致老鼠的食物摄入量和体重减少。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular and Cellular Endocrinology 医学-内分泌学与代谢

CiteScore

9.00

自引率

2.40%

发文量

174

审稿时长

42 days

期刊介绍： Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.