Lateral Septum as a Key Integrative Regulator of Feeding: Role of the Glp-1/Glp-1r System

The control of food intake represents a multifaceted process involving a dynamic interaction between various cerebral regions and peripheral signals. This control incorporates both homeostatic and hedonic systems, contingent upon whether it is responding to nutritional status or to the reward mechanisms associated with food consumption. The lateral septum (LS) functions as a pivotal neural relay center, exerting an effect on alimentary intake upon activation. Due to its extensive neural connections with other cerebral nuclei, the LS is integrated with circuits governing both homeostatic and hedonic feeding controls. Recent investigations have elucidated a connection between the glucagon-like peptide 1 (GLP-1) system and the LS, revealing that the activation of the GLP-1 receptor (GLP-1R) within this region modulates food intake. We present several recent findings highlighting the critical role of the LS in food intake control, alongside the importance of the GLP-1 system within this neural context. Additionally, we advocate for further research on the GLP-1/GLP-1R system in the LS as a therapeutic target for obesity. (Figure presented.). © 2025 International Society for Neurochemistry.