Cuijie Shi

Hunan Normal University

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Yunlong Xu

Sinopec (China)

Gaowei Chen

Shenzhen Institutes of Advanced Technology

Haiyang Jing

Shenzhen Institutes of Advanced Technology

Yingjie Zhu

Chinese Academy of Sciences

Jiafeng Zhong

Shenzhen Institutes of Advanced Technology

Xiaofei Deng

Zhongnan Hospital of Wuhan University

Yu Tian

Hebei Medical University

Yixiao Luo

Guangxi Normal University

Zijun Chen

Beihang University

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Shenzhen Institutes of Advanced Technology

Chinese Academy of Sciences

University of Chinese Academy of Sciences

HKUST Shenzhen Research Institute

City University of Hong Kong

Hebei Medical University

Sinopec (China)

Shenzhen Maternity and Child Healthcare Hospital

Southern Medical University

Donghua University

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GLP-1R–positive neurons in the lateral septum mediate the anorectic and weight-lowering effects of liraglutide in mice

Journal of Clinical Investigation (2024)

Zijun Chen Xiaofei Deng Cuijie Shi Haiyang Jing Yu Tian

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.

Anorectic

10.1172/jci178239

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