侧隔膜中的 GLP-1R 阳性神经元介导了利拉鲁肽对小鼠厌食和降低体重的作用。

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Zijun Chen, Xiaofei Deng, Cuijie Shi, Haiyang Jing, Yu Tian, Jiafeng Zhong, Gaowei Chen, Yunlong Xu, Yixiao Luo, Yingjie Zhu
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引用次数: 0

摘要

利拉鲁肽是一种胰高血糖素样肽-1(GLP-1)类似物,已被批准用于肥胖症治疗,但导致其治疗效果的特定神经元位点仍然难以确定。在这里,我们发现外侧隔的 GLP-1 受体阳性(GLP-1R-positive)神经元(LSGLP-1R)在介导利拉鲁肽的厌食和减肥效应中起着关键作用。LSGLP-1R神经元会被利拉鲁肽强力激活,这些神经元的化学激活会显著抑制进食。有针对性地敲除LS内的GLP-1受体,而不是下丘脑内的GLP-1受体,大大削弱了利拉鲁肽抑制进食和降低体重的能力。在自然进食过程中,LSGLP-1R神经元的活性迅速降低,而LSGLP-1R神经元的突触失活降低了利拉鲁肽引发的厌食效应。总之,这些发现为了解 LSGLP-1R 神经元在能量平衡生理调节中的功能性作用提供了重要见解,并阐明了它们在介导利拉鲁肽药理疗效中的重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
GLP-1R-positive neurons in the lateral septum mediate the anorectic and weight-lowering effects of liraglutide in mice.

Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is approved for obesity treatment, but the specific neuronal sites that contribute to its therapeutic effects remain elusive. Here, we show that GLP-1 receptor-positive (GLP-1R-positive) neurons in the lateral septum (LSGLP-1R) play a critical role in mediating the anorectic and weight-loss effects of liraglutide. LSGLP-1R neurons were robustly activated by liraglutide, and chemogenetic activation of these neurons dramatically suppressed feeding. Targeted knockdown of GLP-1 receptors within the LS, but not in the hypothalamus, substantially attenuated liraglutide's ability to inhibit feeding and lower body weight. The activity of LSGLP-1R neurons rapidly decreased during naturalistic feeding episodes, while synaptic inactivation of LSGLP-1R neurons diminished the anorexic effects triggered by liraglutide. Together, these findings offer critical insights into the functional role of LSGLP-1R neurons in the physiological regulation of energy homeostasis and delineate their instrumental role in mediating the pharmacological efficacy of liraglutide.

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来源期刊
Journal of Clinical Investigation
Journal of Clinical Investigation 医学-医学:研究与实验
CiteScore
24.50
自引率
1.30%
发文量
1034
审稿时长
2 months
期刊介绍: The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science. The journal attracts a diverse readership from various medical disciplines and sectors. It publishes a wide range of research articles encompassing all biomedical specialties, including Autoimmunity, Gastroenterology, Immunology, Metabolism, Nephrology, Neuroscience, Oncology, Pulmonology, Vascular Biology, and many others. The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.
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