Intestinal glucagon-like peptide-1 effects on food intake: Physiological relevance and emerging mechanisms

Abstract

The gut-brain hormone glucagon-like peptide-1 (GLP-1) has received immense attention over the last couple of decades for its widespread metabolic effects. Notably, intestinal GLP-1 has been recognized as an endogenous satiation signal. Yet, the underlying mechanisms and the pathophysiological relevance of intestinal GLP-1 in obesity remain unclear. This review first recapitulates early findings indicating that intestinal GLP-1 is an endogenous satiation signal, whose eating effects are primarily mediated by vagal afferents. Second, on the basis of recent findings challenging a paracrine action of intestinal GLP-1, a new model for the mediation of GLP-1 effects on eating by two discrete vagal afferent subsets will be proposed. The central mechanisms processing the vagal anorexigenic signals need however to be further delineated. Finally, the idea that intestinal GLP-1 secretion and/or effects on eating are altered in obesity and play a pathophysiological role in the development of obesity will be discussed. In summary, despite the successful therapeutic use of GLP-1 receptor agonists as anti-obesity drugs, the eating effects of intestinal GLP-1 still remain to be elucidated. Specifically, the findings presented here call for a further evaluation of the vago-central neuronal substrates activated by intestinal GLP-1 and for further investigation of its pathophysiological role in obesity.

Keywords: Area postrema; Eating; Nucleus of the solitary tract; Obesity; Satiation; Satiety; Vagal afferent neurons.