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 KATP/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. GLP‐1 regulates synaptic transmission in the central nervous system and thus contributes to mediating energy homeostasis. Here we review the effect of GLP‐1 on synaptic transmission in different regions including hippocampus, hypothalamus, brain stem, and vagal nervous. We attempt to provide mechanistic insights into how GLP‐1 functions in the central nervous system.