The Role of Metabolite-Sensing G Protein-Coupled Receptors in Inflammation and Metabolic Disease.
Recio C., Lucy D., Iveson P., Iqbal AJ., Valaris S., Wynne G., Russell AJ., Choudhury RP., O'Callaghan C., Monaco C., Greaves DR.
SIGNIFICANCE: Great attention has been placed on the link between metabolism and immune function giving rise to the term "immunometabolism." It is widely accepted that inflammation and oxidative stress are key processes that underlie metabolic complications during obesity, diabetes, and atherosclerosis. Therefore, identifying the mechanisms and mediators that are involved in the regulation of both inflammation and metabolic homeostasis is of high scientific and therapeutic interest. Recent Advances: G protein-coupled receptors (GPCRs) that signal in response to metabolites have emerged as attractive therapeutic targets in inflammatory disease. Critical Issues and Future Directions: In this review, we discuss recent findings about the physiological role of the main metabolite-sensing GPCRs, their implication in immunometabolic disorders, their principal endogenous and synthetic ligands, and their potential as drug targets in inflammation and metabolic disease. Antioxid. Redox Signal. 00, 000-000.