Glucagon-Like Peptide-1 Receptor in the Brain: Role in Neuroendocrine Control of Energy Metabolism and Treatment Target for Obesity

The central glucagon‐like peptide (GLP)‐1 receptor mediates a number of metabolic processes, including feeding, body weight and glucose homeostasis. More recently, roles in energy expenditure and reward pathway modulation have been described. GLP‐1 receptor agonism promotes insulin release and is currently used to treat type 2 diabetes humans, with a common side effect being weight loss. It is likely that many of these metabolic effects are mediated by GLP‐1Rs located in the central nervous system, throughout areas known to be important in control of energy homeostasis. The physiological role of the GLP‐1 receptor signalling in each of these brain nuclei is becoming clearer and the GLP‐1 system appears to act as an integrator of peripheral energy availability and effector of metabolic regulation. This makes it an attractive target for obesity therapies, with excellent pre‐clinical efficacy seen in molecules combining GLP‐1 receptor agonism with glucagon receptor agonism. This review discusses what is known about the functions of the GLP‐1 receptor in the central nervous system, and highlights the ways that this system may be targeted for development of new obesity therapeutics.