GLP-1R-positive Neurons in the Lateral Septum Mediate the Anorectic and Weight-lowering Effects of Liraglutide in Mice

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2024 Sep 3

PMID 39225090

Authors

Zijun Chen

Xiaofei Deng

Cuijie Shi

Haiyang Jing

Yu Tian

Jiafeng Zhong

Gaowei Chen

Yunlong Xu

Yixiao Luo

Yingjie Zhu

Affiliations

Soon will be listed here.

Abstract

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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