Emerging roles of spexin in cardiovascular homeostasis

Spexin (SPX) is a highly conserved, proteolytically processed 14-amino acid peptide hormone derived from spexin precursor, originally identified through a bioinformatics-based prediction algorithm. SPX possesses pleiotropic effects across multiple organ system and has been implicated in the regulation of appetite, lipid and glucose metabolism, reproduction, inflammation, oxidative stress, neuropsychiatric functions, and cardiovascular physiology, with emerging evidence indicating sex-dependent effects in reproduction and metabolism. SPX exerts its biological effects via galanin receptors, engaging diverse G-protein coupled receptor signaling pathways. Altered SPX expression has been observed in a range of metabolic and systemic conditions, including obesity and metabolic syndrome, type 2 diabetes, hypertension, anxiety and depression, chronic kidney disease, non-alcoholic fatty liver disease, and aging, among others, highlighting its potential as both a diagnostic biomarker and a therapeutic target. Recent research suggests that SPX contributes to cardiovascular homeostasis by modulating autonomic regulation, inflammatory response, cardiomyocyte apoptosis, vascular tone, carotid body chemoreception, lipid metabolism, and insulin sensitivity, all of which are critical for maintaining cardiovascular health. This review concisely summarizes the distribution and regulation of SPX, with a focus on its emerging roles in the pathogenesis of cardiovascular disease and its potential as a theranostic agent.