# Emerging roles of spexin in cardiovascular homeostasis **Authors:** Shuyun Wang, Jiangkang Xie, Zelin Li, Liang Mao, Xitong Dang PMC · DOI: 10.3389/fcvm.2026.1704813 · Frontiers in Cardiovascular Medicine · 2026-02-18 ## TL;DR Spexin is a hormone involved in regulating various body functions, including cardiovascular health, and may serve as a potential diagnostic and therapeutic tool. ## Contribution This review highlights spexin's emerging roles in cardiovascular homeostasis and its potential as a theranostic agent. ## Key findings - Spexin modulates autonomic regulation, inflammation, and vascular tone to support cardiovascular health. - Altered spexin levels are linked to conditions like hypertension, diabetes, and metabolic syndrome. - Spexin signaling through galanin receptors influences cardiomyocyte apoptosis and lipid metabolism. ## Abstract 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. ## Linked entities - **Proteins:** SPX (spexin hormone) - **Diseases:** obesity (MONDO:0011122), metabolic syndrome (MONDO:0000816), type 2 diabetes (MONDO:0005148), anxiety (MONDO:0005618), depression (MONDO:0002050), chronic kidney disease (MONDO:0005300), non-alcoholic fatty liver disease (MONDO:0013209) ## Full-text entities - **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, KCNN4 (potassium calcium-activated channel subfamily N member 4) [NCBI Gene 3783] {aka DHS2, IK, IK1, IKCA1, KCA4, KCa3.1}, TFAM (transcription factor A, mitochondrial) [NCBI Gene 7019] {aka MTDPS15, MTTF1, MTTFA, TCF6, TCF6L1, TCF6L2}, Spx (spexin hormone) [NCBI Gene 319552] {aka B230216G23Rik, Npq}, SLN (sarcolipin) [NCBI Gene 6588], CRH (corticotropin releasing hormone) [NCBI Gene 1392] {aka CRF, CRH1}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, LEPR (leptin receptor) [NCBI Gene 3953] {aka CD295, LEP-R, LEPRD, OB-R, OBR, huB219}, CEBPB (CCAAT enhancer binding protein beta) [NCBI Gene 1051] {aka C/EBP-beta, IL6DBP, NF-IL6, TCF5}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, GALR1 (galanin receptor 1) [NCBI Gene 2587] {aka GALNR, GALNR1}, CPT1A (carnitine palmitoyltransferase 1A) [NCBI Gene 1374] {aka CPT I, CPT1, CPT1-L, CPTI-L, L-CPT1}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MMP14 (matrix metallopeptidase 14) [NCBI Gene 4323] {aka MMP-14, MMP-X1, MT-MMP, MT-MMP 1, MT1-MMP, MT1MMP}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, SPX (spexin hormone) [NCBI Gene 80763] {aka C12orf39, SPX1}, MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322] {aka CLG3, MANDP1, MDST, MMP-13}, Becn1 (beclin 1, autophagy related) [NCBI Gene 56208] {aka Atg6}, GALR2 (galanin receptor 2) [NCBI Gene 8811] {aka GAL2-R, GALNR2, GALR-2}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, Crh (corticotropin releasing hormone) [NCBI Gene 81648] {aka CRF}, POU2F1 (POU class 2 homeobox 1) [NCBI Gene 5451] {aka OCT1, OTF1, Oct1Z, oct-1B}, CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 820] {aka CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26}, ECRG4 (ECRG4 augurin precursor) [NCBI Gene 84417] {aka C2orf40}, CRHR2 (corticotropin releasing hormone receptor 2) [NCBI Gene 1395] {aka CRF-RB, CRF2, CRFR2, HM-CRF}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, GALR3 (galanin receptor 3) [NCBI Gene 8484], CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, CXCR6 (C-X-C motif chemokine receptor 6) [NCBI Gene 10663] {aka BONZO, CD186, CDw186, STRL33, TYMSTR}, LPAR2 (lysophosphatidic acid receptor 2) [NCBI Gene 9170] {aka EDG-4, EDG4, LPA-2, LPA2}, KCNJ2 (potassium inwardly rectifying channel subfamily J member 2) [NCBI Gene 3759] {aka ATFB9, HHBIRK1, HHIRK1, IRK1, KIR2.1, LQT7}, UCP2 (uncoupling protein 2) [NCBI Gene 7351] {aka BMIQ4, SLC25A8, UCPH}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, Spx (spexin hormone) [NCBI Gene 691138] {aka Npq}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, ACADM (acyl-CoA dehydrogenase medium chain) [NCBI Gene 34] {aka ACAD1, MCAD, MCADH}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, Th (tyrosine hydroxylase) [NCBI Gene 25085] {aka The}, NPY (neuropeptide Y) [NCBI Gene 4852] {aka PYY4}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}, GAL (galanin and GMAP prepropeptide) [NCBI Gene 51083] {aka ETL8, GAL-GMAP, GALN, GLNN, GMAP}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1} - **Diseases:** weight gain (MESH:D015430), STEMI (MESH:D000072657), obese (MESH:D009765), hypoxic (MESH:D002534), chest pain (MESH:D002637), overweight (MESH:D050177), SCD (MESH:D016757), cardiotoxicity (MESH:D066126), cardiac ischemia (MESH:D007511), metabolic dysregulation (MESH:D021081), metabolic (MESH:D008659), renal IRI (MESH:D006030), hypoxia (MESH:D000860), Disease (MESH:D004194), brain and liver complications (MESH:D008107), Inflammation (MESH:D007249), fibrosis (MESH:D005355), MS (MESH:D024821), hyperglycemia (MESH:D006943), hyperoxia (MESH:D018496), dyslipidemia (MESH:D050171), mitochondrial (MESH:D028361), non-alcoholic fatty liver disease (MESH:D065626), Diabetes (MESH:D003920), tumor (MESH:D009369), Prediabetes (MESH:D011236), DM (MESH:D009223), chronic kidney disease (MESH:D051436), anxiety (MESH:D001007), type 2 diabetes (MESH:D003924), infarct (MESH:D007238), depression (MESH:D003866), adiposity (MESH:D018205), injured kidney (MESH:D007674), systemic (MESH:D015619), anorexia nervosa (MESH:D000856), appetite (MESH:D001068), diabetic nephropathy (MESH:D003928), hyperuricemia (MESH:D033461), myocardial necrosis (MESH:D009336), lipid abnormalities (MESH:D011017), chronic (MESH:D002908), vascular calcification (MESH:D061205), MIRI (MESH:D015427), PCOS (MESH:D011085), Hypertension (MESH:D006973), IGR (MESH:C565631), hyperinsulinemia (MESH:D006946), atherogenic (MESH:D050197), AMI (MESH:D009203), CVD (MESH:D002318), AF (MESH:D001281), Myocardial ischemia (MESH:D017202), chronic renal failure (MESH:D007676), vascular damage (MESH:D057772), toxicity (MESH:D064420), weight loss (MESH:D015431), IR (MESH:D007333) - **Chemicals:** advanced glycation end products (MESH:D017127), iron (MESH:D007501), testosterone (MESH:D013739), streptozotocin (MESH:D013311), adenine (MESH:D000225), cholesterol (MESH:D002784), nitric oxide (MESH:D009569), cyclic adenosine monophosphate (MESH:D000242), fat (MESH:D005223), VITD (MESH:D014807), oxygen (MESH:D010100), E2 (MESH:D004958), cortisol (MESH:D006854), escitalopram (MESH:D000089983), DHEA-S (MESH:D019314), triglycerides (MESH:D014280), citalopram (MESH:D015283), fructose (MESH:D005632), isoproterenol (MESH:D007545), ATP (MESH:D000255), glutathione (MESH:D005978), carbon dioxide (MESH:D002245), steroid hormone (MESH:D013256), lipid (MESH:D008055), sodium nitroprusside (MESH:D009599), glucose (MESH:D005947), 5-HT (MESH:D012701), creatinine (MESH:D003404), calcium (MESH:D002118), ROS (MESH:D017382), AA53-70 (-), CUR (MESH:D003474), palmitate (MESH:D010168), NO (MESH:D009614), nerolidol (MESH:C037055), DOX (MESH:D004317), urea (MESH:D014508), fatty acid (MESH:D005227), carbohydrate (MESH:D002241) - **Species:** Carassius auratus (goldfish, species) [taxon 7957], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Rodentia (rodent, order) [taxon 9989], Homo sapiens (human, species) [taxon 9606] - **Cell lines:** H9C2 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0286) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12957216/full.md ## Figures 1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12957216/full.md ## References 103 references — full list in the complete paper: https://tomesphere.com/paper/PMC12957216/full.md --- Source: https://tomesphere.com/paper/PMC12957216