Brain-Derived GLP-1—Understanding the Physiological Function and Anti-obesity Potential of Preproglucagon Neurons

Glucagon-like peptide-1 (GLP-1) is produced within the central nervous system (CNS) by preproglucagon (PPG) neurons. This brain-derived GLP-1, rather than that released from the gut, is the physiological agonist for brain GLP-1 receptors (GLP-1Rs). With brain GLP-1Rs being a major target for eating suppression, understanding the physiology and the translational potential of PPG neurons is of pivotal importance, particularly since PPG neuron activation is also strongly associated with stress. This review critically summarizes the current knowledge of PPG neuron anatomy, physiology, and molecular makeup together with insight into the relevant research tools, and consideration of the different PPG neuron populations within the CNS, to provide an appraisal of the potential of these neurons as drug targets and the associated risks and benefits.