The Emerging Roles of Metabolite-Activated GPCRs in Teleost Physiology and Aquaculture Development

Metabolites, once viewed mainly as energy substrates or structural precursors, are now increasingly recognized as key extracellular signaling mediators that regulate diverse physiological processes. This review synthesizes and systematizes current knowledge on metabolite-mediated signaling through G-protein-coupled receptors (GPCRs) in teleosts and, importantly, highlights new conceptual links between specific metabolite-GPCR axes and key physiological functions relevant to aquaculture. By integrating evidence across metabolite-GPCRs axes, including succinate-SUCNR1, aromatic amino acids (tryptophan and phenylalanine)-GPR142, basic amino acids (L-arginine)-GPRC6A, and lactate-GPR81. We clarify how metabolite-receptor interactions have the potential to modulate glucose homeostasis, immune responses, energy metabolism, and stress coping. A major contribution of this review is illustrating how metabolites act not only as nutrients but also as extracellular signaling molecules governing core physiological processes via GPCRs. Particularly from an evolutionary perspective, compared with peptide-activated GPCRs, metabolite-sensing GPCRs are relatively conserved across different species, suggesting that relevant findings from biomedical research could be translated to aquaculture applications. Therefore, understanding GPCR-mediated metabolite sensing provides a molecular foundation for improving nutrient formulation, developing functional feeds, and designing selective breeding strategies in precision aquaculture.