The GLP ‐1– miRNA network: Epigenetic control of obesity and metabolic disorders

Glucagon-like peptide-1 (GLP-1) is a central incretin hormone with pleiotropic effects on glucose homeostasis, appetite regulation, and energy metabolism. Beyond its classical insulinotropic actions, GLP-1 enhances cardiovascular, renal, hepatic, and central nervous system (CNS) functions, thereby integrating multi-organ metabolic responses. Emerging evidence highlights the critical role of microRNAs (miRNAs) as epigenetic regulators of GLP-1 signalling, influencing receptor expression, β-cell survival, hypothalamic appetite circuits, and peripheral tissue metabolism. miRNAs act bidirectionally: they can attenuate GLP-1 receptor (GLP-1R) expression, contributing to 'incretin resistance' in obesity and type 2 diabetes (T2DM), or mediate GLP-1-induced transcriptional adaptations that enhance insulin secretion, lipid oxidation, and energy expenditure. This review synthesizes current knowledge of GLP-1 physiology, receptor signalling, and the miRNA-mediated regulatory network, with a focus on mechanisms underlying obesity and metabolic disorders. This review proposes an integrated GLP-1-miRNA framework that bridges molecular endocrinology with precision metabolic medicine.