Neuronatin in Metabolic Regulation: Molecular Interplay in Obesity and Type 2 Diabetes Pathogenesis

Growing evidence has established the imprinted gene neuronatin (NNAT) as a key regulator in human metabolic disorders, particularly obesity and type 2 diabetes. Its expression is prominently detected in major neuroendocrine and metabolic tissues, including the hypothalamus, pancreas, adipose tissue, and skeletal muscle. NNAT orchestrates diverse cellular processes through its regulation of intracellular calcium dynamics and pathological insulin secretion. Notably, NNAT exhibits nutrient-responsive regulation and is a crucial modulator of glucose homeostasis, adaptive thermogenesis, and overall energy balance. These pleiotropic functions position NNAT as an attractive therapeutic target for obesity-related metabolic disorders. This comprehensive review systematically evaluates the multifaceted roles of NNAT in metabolic regulation, with a particular focus on its tissue-specific mechanisms in both physiological and pathological states while integrating the current understanding of its contributions to systemic metabolic homeostasis.