Gprc6a, a G-protein coupled receptor, is proposed to be a master regulator of complex endocrine networks and metabolic processes. It is activated by multiple ligands like osteocalcin (Ocn), testosterone (T), basic amino acids, and various cations. It has been implicated in coordinating the secretion of hormones such as insulin, GLP-1, T, and IL-6, and directly controls glucose and fat metabolism in the liver, skeletal muscle, and fat [1].

Global deletion of Gprc6a in mice results in a metabolic syndrome-like phenotype, including obesity, glucose intolerance, hepatic steatosis, insulin resistance, hyperphosphatemia, and osteopenia, along with hormonal abnormalities [5]. Adipocyte-specific Gprc6a knockout mice show increased adipose tissue weight, adipocyte hypertrophy, and adipose tissue inflammation when fed a high-fat and high-sucrose diet, due to reduced lipolytic activity [3]. Hepatocyte-specific Gprc6a knockout mice have excessive hepatic fat accumulation, glycogen depletion, and impaired glucose and pyruvate tolerance [4].

In conclusion, Gprc6a plays a crucial role in regulating energy metabolism, including glucose and fat metabolism, as well as maintaining amino acid homeostasis. The gene knockout mouse models have revealed its significance in metabolic syndrome-related diseases, suggesting it may be a potential target for treating disordered energy metabolism, metabolic syndrome, and type 2 diabetes [2,3,4].