Host metabolite-sensing receptors

Host metabolite-sensing receptors are a broad category of proteins, primarily G protein-coupled receptors (GPCRs) and nuclear receptors, that detect endogenous and microbiota-derived metabolites to regulate physiological homeostasis (PubMed: 25662522). This class includes the free fatty acid receptors (FFARs), bile acid receptors such as Farnesoid X receptor (FXR) and TGR5, and hydroxycarboxylic acid receptors (HCARs) (UniProt: P32249, Q96P67). These receptors function as molecular sensors that translate chemical signals from the diet and gut microbiome into cellular responses, influencing glucose metabolism, lipid storage, and immune cell activity (PubMed: 12711604). Dysregulation of these pathways is linked to metabolic syndrome, type 2 diabetes, and chronic inflammatory diseases like inflammatory bowel disease (PubMed: 21079686). Therapeutic targeting of these receptors involves the use of small-molecule agonists or antagonists, such as obeticholic acid for FXR or fibrates for PPARs, to restore metabolic balance. However, the wide tissue distribution of these receptors often presents challenges related to off-target effects and systemic toxicity (PubMed: 29453248).

Other names

Metabolite-sensing GPCRsNutrient-sensing receptorsMetabolic sensorsSurface metabolite receptors

Activation or inhibition of specific G protein-coupled receptors or nuclear receptors to modulate metabolic and inflammatory signaling pathways.