Glucagon-like peptide-1 drives energy metabolism on the synaptic highway

Glucagon-like peptide-1 (GLP-1), a gut–brain hormone, coordinates energy balance in both peripheral organs and the central nervous system (CNS). In the pancreas, GLP-1 facilitates insulin exocytosis or suppresses glucagon exocytosis via multiple pathways such as regulating K_ATP/Kv channels, N-type Ca²⁺ channels, and the readily releasable pool. In the CNS, GLP-1 signaling regulates neuronal excitability in various brain regions, including neurons in the hippocampus, hypothalamus, and mesolimbic systems. GLP-1 modulation on synaptic transmission includes both pre- and postsynaptic pathways that are either excitatory or inhibitory. Synaptic transmission conveys information flow in the brain and governs brain-mediated behaviors. The study of GLP-1 control of energy metabolism at a synaptic level may shed light on the role of GLP-1 function in the brain. Various challenges remain including defining the mechanism of GLP-1 release in the brain.