Abstract
Abstract 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.
Highlights
Incretins are gut hormones that facilitate insulin secretion upon food ingestion in a glucose-dependent manner
We suggest that glucose-dependent insulinotropic peptide (GIP)-induced TG storage capacity in white adipocytes is a protective mechanism under nutrient excess, since White adipose tissue (WAT) is the organ best suited for fat storage, unlike liver or muscle where TG storage causes insulin resistance
This is profoundly evident during obesity, when pathological immune cell activities at sites such as the brain and WAT alter homeostatic metabolic pathways that are in charge of controlling body weight, glucose concentration and energy expenditure
Summary
Incretins are gut hormones that facilitate insulin secretion upon food ingestion in a glucose-dependent manner. Receptors for GLP-1 and GIP are found on different immune cell populations, suggesting in addition direct immunoregulatory roles for these metabolic hormones. We aim to provide an up-to-date view of the immunoregulatory properties of these incretin hormones and their potential impact on physiological metabolic actions To this end, we first describe the recent advances in our comprehension of immune cell networks in adipose tissue and brain, and their concerted modulation of organ-specific metabolic pathways in health and disease. We first describe the recent advances in our comprehension of immune cell networks in adipose tissue and brain, and their concerted modulation of organ-specific metabolic pathways in health and disease This is followed by a brief description of the key metabolic activities of GLP-1 and GIP. There is reasonable data to suggest that incretin-based therapeutic agents have an anti-inflammatory effect in addition to their ability to regulate blood glucose, which may provide additional benefits in the treatment of T2DM
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