Glucagon-like peptide-1 receptor in the brain: role in neuroendocrine control of energy metabolism and treatment target for obesity

Abstract

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.