Incretin Hormones in the Control of Immunometabolism

Incretin peptides, mainly glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are gut derived hormones secreted upon cues from ingested food that regulate glucose concentration, lipid metabolism and gut motility. The classic role of incretins is to convey the status of nutrient availability from the gut to the brain, initiating changes in eating behavior and energy expenditure to maintain body weight. Incretins also act directly on metabolically important peripheral targets in a highly concerted fashion to maintain energy balance and glucose homeostasis. As a result, a myriad of therapeutics for metabolic diseases based on the actions of incretins, particularly GLP-1, are currently under clinical development. Multiple immune cell subsets express receptors for GLP-1 and GIP, but their immunoregulatory roles remain incompletely understood. Innate and adaptive immune cells are intertwined in the homeostatic regulation of central and peripheral metabolism and energy balance, but also contribute to their impairment in the context of metabolic syndrome-related diseases. Hence, delineating the cellular and signaling networks by which incretins operate at the immunometabolic interface has a remarkable translational relevance. In this review, we concisely describe the well-characterized metabolic functions of GLP-1 and GIP, and offer an unprecedented view on the ability of these hormones to modulate immune responses via their direct action on immune cells.