GPR84 in physiology—Many functions in many tissues

Abstract

Members of the GPCR superfamily have a wide variety of physiological roles and are therefore valuable targets for developing effective medicines. However, within this superfamily are receptors that are less well characterised and remain orphans, including GPR84. This receptor, is stimulated by ligands derived from dietary nutrients, specifically medium chain fatty acids (MCFAs), and novel synthetic agonists. There is data demonstrating the role of GPR84 in inflammatory pathways, in addition to emerging data suggesting a key role for GPR84 as a nutrient‐sensing GPCR involved in metabolism by sensing energy load via nutrient exposure and subsequent signalling leading to modulation of food intake. Exploring GPR84 pharmacology, its localisation and what drives its expression reveals multiple roles for this receptor. Here, we will reflect on these various roles of GRP84 demonstrated thus far, primarily by exploring data from pre‐clinical and clinical studies in various physiological systems, with a specific focus on the gastrointestinal tract.

Editorial for GPR84 pharmacology

“…In moving away from immune cell function, Madusha Peiris (Queen Mary University of London) instead focused on the expression and function of GPR84 in enteroendocrine cells of the gut and the concept that regulation of gut hormone release could be enhanced by co-stimulation of GPR84 (Aktar et al, 2024). Indeed, Peiris highlighted beneficial effects of dietary supplementation with the C10 MCFA decanoic acid in lowering plasma glucose, total cholesterol levels and decreasing food intake, effects lacking in GPR84 knock-out mice.…”

CuO nanoparticles elicit intestinal immunotoxicity in zebrafish based on intestinal microbiota dysbiosis

“…Food & Function responses. 49 The activation of GPR84 has been shown to elevate the expression levels of pro-inflammatory factors and reduce the release of anti-inflammatory cytokines. [50][51][52] Indeed, SCFAs not only serve as an energy source but also can act as signaling factors through GPCRs.…”