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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\u2010responsive 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\u2010related metabolic disorders. This comprehensive review systematically evaluates the multifaceted roles of NNAT in metabolic regulation, with a particular focus on its tissue\u2010specific mechanisms in both physiological and pathological states while integrating the current understanding of its contributions to systemic metabolic homeostasis.<\/jats:p>","DOI":"10.1002\/jcp.70119","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:13:28Z","timestamp":1765203208000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuronatin in Metabolic Regulation: Molecular Interplay in Obesity and Type 2 Diabetes Pathogenesis"],"prefix":"10.1002","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3473-956X","authenticated-orcid":false,"given":"Ting","family":"Zhang","sequence":"first","affiliation":[{"name":"Center of Obesity and Metabolic Diseases, Department of General Surgery Affiliated Hospital of 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