{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSpexin (SPX), also known as neuropeptide Q (NPQ), was initially discovered using bioinformatics and evolutionary genomics approaches. These studies revealed that SPX shares sequence similarities and genomic clustering with the galanin and kisspeptin peptide gene families, and that it preferentially activates the galanin receptor subtypes GALR2/3. In addition to these molecular relationships, SPX has been shown to exert renal, cardiovascular, and antinociceptive effects while also inhibiting food intake and lipid absorption, which may contribute to reductions in body weight and improvements in insulin sensitivity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of metabolic regulation in adults, SPX is widely expressed in endocrine tissues and adipocytes and appears to play an important role in energy homeostasis. Lower circulating levels of SPX have been consistently associated with obesity, insulin resistance, and adverse lipid profiles. Experimental studies document that SPX exerts direct actions on adipocytes by inhibiting adipogenesis and lipogenesis while simultaneously stimulating lipolysis. These findings indicate that SPX not only serves as a regulator of gluco‐lipid metabolism but also holds promise as a biomarker and potential therapeutic target in metabolic syndrome and weight-loss interventions such as bariatric surgery."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn pediatric populations and during gestation, the role of SPX is less clear and appears to be context dependent. While initial reports suggest that this peptide may be implicated in the regulation of obesity and energy balance in children, some studies in adolescents and newborns have failed to reveal significant correlations between SPX levels and metabolic parameters. In gestational settings, alterations in SPX concentrations have been observed in patients with gestational diabetes mellitus (GDM) – with some studies reporting increased levels associated with insulin resistance and others noting minimal effects on intrauterine growth – underscoring the complexity of SPX dynamics during development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "18"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its peripheral metabolic actions, SPX is also expressed in the central nervous system where it is localized to key neurosecretory regions such as the supraoptic and paraventricular nuclei – regions known to mediate control of osmotic balance, food intake, and reproductive functions. In the ovary, SPX has been shown to reduce granulosa cell proliferation and steroidogenesis, suggesting a potential role in the pathophysiology of disorders such as polycystic ovarian syndrome (PCOS). Moreover, emerging evidence indicates that SPX may exert neuroprotective and antinociceptive effects, as lower levels have been linked to diabetic peripheral neuropathy and pain in patients with type 2 diabetes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "21"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lawrence Toll, Taline V Khroyan, Kemal Sonmez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Peptides derived from the prohormone proNPQ/spexin are potent central modulators of cardiovascular and renal function and nociception."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.11-192831"}], "href": "https://doi.org/10.1096/fj.11-192831"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22038051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22038051"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dong-Kyu Kim, Seongsik Yun, Gi Hoon Son, et al. 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