Roles of Nutrition-Sensing Receptor GPRC6A in Energy Metabolism and Oral Inflammatory Diseases

G protein-coupled receptor class C group 6 member A (GPRC6A) is widely expressed in various tissues and is essential for whole-body homeostasis. In this review, we aimed to discuss the roles of GPRC6A as a nutrient sensor.

GPRC6A is highly expressed in metabolic tissues and serves as a key nutrient sensor. It is activated by various ligands, including basic amino acids, divalent cations, a bone-derived hormone osteocalcin, and testosterone. GPRC6A integrates glucose and lipid metabolism by detecting the changes in hormone and blood amino acid levels in response to alterations in nutritional status. Additionally, GPRC6A activates the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome via Ca²⁺ signaling, potentially contributing to the progression of periodontal diseases. Elevated extracellular Ca²⁺ at the inflammation site activates the NLRP3 inflammasome via GPRC6A, leading to interleukin-1β release and enhanced inflammatory responses. NLRP3 inflammasome activation further correlates with disease severity.

GPRC6A is crucial for the regulation of energy metabolism and inflammation, making it a potential therapeutic target.