The diverse effects of brain glucagon-like peptide 1 receptors on ingestive behaviour

Abstract

Glucagon-like peptide 1 (GLP-1) is well known as a gut hormone and also acts as a neuropeptide, produced in a discrete population of caudal brainstem neurons that project widely throughout the brain. GLP-1 receptors are expressed in many brain areas of relevance to energy balance, and stimulation of these receptors at many of these sites potently suppresses food intake. This review surveys the current evidence for effects mediated by GLP-1 receptors on feeding behaviour at a wide array of brain sites and discusses behavioural and neurophysiological mechanisms for the effects identified thus far. Taken together, it is clear that GLP-1 receptor activity in the brain can influence feeding by diverse means, including mediation of gastrointestinal satiation and/or satiety signalling, suppression of motivation for food reward, induction of nausea and mediation of restraint stress-induced hypophagia, but many questions about the organization of this system remain. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.

Keywords: GLP-1; feeding behavior; food reward; gut-brain communication; satiation; satiety.

FIGURE 1

Diagram of a sagittal section of rodent brain showing the brain nuclei where GLP‐1 receptors have been shown to affect food intake. Blue ovals represent those at which GLP‐1 receptor agonist application suppresses feeding, whereas red ovals represent those at which both (1) GLP‐1 receptor agonist application suppresses feeding and (2) antagonist injection or receptor knockdown increases feeding, providing evidence that endogenous GLP‐1 receptor stimulation at these sites plays a role in feeding control

FIGURE 2

Summary of behavioural mechanisms through which brain GLP‐1 receptors (GLP‐1R) appear to suppress food intake (amplifying satiation; suppressing food reward; inducing nausea; and promoting stress responses), along with the brain areas implicated in each of these types of responses thus far. *GLP‐1 receptor stimulation in the central nucleus of the amygdala (CeA) appears to induce nausea without hypophagia