GPER in metabolic homeostasis and disease: molecular mechanisms, nutritional regulation, and therapeutic potential.

G protein-coupled estrogen receptor (GPER) significantly influences metabolic regulation by engaging multiple signaling pathways that affect overall metabolic health. Its structure and signaling mechanisms drive its diverse roles. Our team and others have successfully demonstrated that GPER modulates nutrient metabolism, spanning glucose, protein, and lipid metabolism, while also contributing to vitamin and mineral metabolism. Studies have linked GPER to metabolic disorders, including type 2 diabetes, nonalcoholic fatty liver disease, metabolic syndrome, and cardiovascular diseases, as well as thyroid disorders, highlighting its wide-reaching metabolic impact. GPER holds promise for energy balance and weight management by regulating energy expenditure and thermogenesis. Moreover, it appears to influence the metabolism of cancer cells during tumor progression. Rapid advancements in GPER agonist and antagonist research have highlighted the therapeutic potential of GPER agonists for treating metabolic diseases. Further investigations into GPER biology, mechanisms, and clinical applications will support novel therapeutic strategies, establishing GPER as a key target in metabolic research and treatment.