Hunting for heroes: Brain neurons mediating GLP-1R agonists in obesity treatment

Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) have proven to be highly effective in reducing obesity across species and ages, gaining unmet popularity in clinical treatments against obesity. Although extensive research efforts have been made to explore how the brain regulates body weight homeostasis including the effect brought up by GLP-1 and its synthetic analogs GLP-1RAs, the identity of neurons and neural pathways that are responsible for the observed anti-obesity effect of GLP-1RAs remain largely elusive. Excitingly, three recent high-profile studies presented compelling evidence that each argues for the importance of GLP-1Rs in the dorsomedial hypothalamus, hindbrain, or lateral septum, respectively, in mediating the anti-obesity effect of GLP-1RAs. While these studies clearly illustrated the contributions of each of these distinct brain regions involved in GLP-1RAs in body weight regulation, the presented results also suggest the complexity of the involved brain neural network. This commentary briefly introduces these studies and highlights key knowledge gaps that require further investigation.