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Physiology and Biochemistry

Novel insights on the role of spexin as a biomarker of obesity and related cardiometabolic disease

International Journal of Obesity volume 45, pages 2169–2178 (2021)Cite this article

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Abstract

Spexin (SPX) is a 14-amino acid neuropeptide, discovered recently using bioinformatic techniques. It is encoded by the Ch12:orf39 gene that is widely expressed in different body tissues/organs across species, and secreted into systemic circulation. Recent reports have highlighted a potentially important regulatory role of SPX in obesity and related comorbidities. SPX is also ubiquitously expressed in human tissues, including white adipose tissue. The circulating concentration of SPX is significantly lower in individuals with obesity compared to normal weight counterparts. SPX’s role in obesity appears to be related to various factors, such as the regulation of energy expenditure, appetite, and eating behaviors, increasing locomotion, and inhibiting long-chain fatty acid uptake into adipocytes. Recent reports have also suggested SPX’s relationship with novel biomarkers of cardiovascular disease (CVD) and glucose metabolism and evoked the potential role of SPX as a key biomarker/player in the early loss of cardiometabolic health and development of CVD and diabetes later in life. Data on age-related changes in SPX and SPX’s response to various interventions are also emerging. The current review focuses on the role of SPX in obesity and related comorbidities across the life span, and its response to interventions in these conditions. It is expected that this article will provide new ideas for future research on SPX and its metabolic regulation, particularly related to cardiometabolic diseases.

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Fig. 1: A conceptual model of SPX regulation by age, obesity and related metabolic changes, and potential modulation by lifestyle-based interventions.

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References

  1. Skinner AC, Ravanbakht SN, Skelton JA, Perrin EM, Armstrong SC. Prevalence of obesity and severe obesity in US children, 1999-2016. Pediatrics. 2018;141:3.

    Article  Google Scholar 

  2. Ward ZJ, Bleich SN, Cradock AL, Barrett JL, Giles CM, Flax C, et al. Projected US state-level prevalence of adult obesity and severe obesity. N Engl J Med. 2019;381:2440–50.

    Article  PubMed  Google Scholar 

  3. Skinner AC, Perrin EM, Skelton JA. Cardiometabolic risks and obesity in the young. N Engl J Med. 2016;374:592–3.

    PubMed  Google Scholar 

  4. Eckel RH, Blaha MJ. Cardiometabolic medicine: a call for a new subspeciality training track in internal medicine. Am J Med. 2019;132:788–90.

    Article  PubMed  Google Scholar 

  5. Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Houston Miller N, Hubbard VS, et al. AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014. 2013;129:S76–99.

    Google Scholar 

  6. Ryder JR, Xu P, Inge TH, Xie C, Jenkins TM, Hur C, et al. Thirty-year risk of cardiovascular disease events in adolescents with severe. Obesity. 2020;28:616–23.

    Article  PubMed  Google Scholar 

  7. Kelly AS, Barlow SE, Rao G, Inge TH, Hayman LL, Steinberger J, et al. Severe obesity in children and adolescents: identification, associated health risks, and treatment approaches: a scientific statement from the American Heart Association. Circulation. 2013;128:1689–712.

    Article  PubMed  Google Scholar 

  8. Balagopal PB, de Ferranti SD, Cook S, Daniels SR, Gidding SS, Hayman LL, et al. Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association. Circulation. 2011;123:2749–69.

    Article  PubMed  Google Scholar 

  9. Daniels SR, Pratt CA, Hollister EB, Labarthe D, Cohen DA, Walker JR, et al. Promoting cardiovascular health in early childhood and transitions in childhood through adolescence: a workshop report. J Pediatr. 2019;209:e1–251.

    Article  Google Scholar 

  10. Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation. 2006;113:2335–62.

    Article  PubMed  Google Scholar 

  11. Eckel RH, Kahn R, Robertson RM, Rizza RA. Preventing cardiovascular disease and diabetes: a call to action from the American Diabetes Association and the American Heart Association. Circulation. 2006;113:2943–6.

    Article  PubMed  Google Scholar 

  12. Dhingra R, Vasan RS. Biomarkers in cardiovascular disease: statistical assessment and section on key novel heart failure biomarkers. Trends Cardiovasc Med. 2017;27:123–33.

    Article  CAS  PubMed  Google Scholar 

  13. Mirabeau O, Perlas E, Severini C, Audero E, Gascuel O, Possenti R, et al. Identification of novel peptide hormones in the human proteome by hidden Markov model screening. Genome Res. 2007;17:320–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Walewski JL, Ge F, Gagner M, Inabnet WB, Pomp A, Branch AD, et al. Adipocyte accumulation of long-chain fatty acids in obesity is multifactorial, resulting from increased fatty acid uptake and decreased activity of genes involved in fat utilization. Obes Surg. 2010;20:93–107.

    Article  PubMed  Google Scholar 

  15. Porzionato A, Rucinski M, Macchi V, Stecco C, Malendowicz LK, De Caro R. Spexin expression in normal rat tissues. J Histochem Cytochem. 2010;58:825–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gu L, Ma Y, Gu M, Zhang Y, Yan S, Li N, et al. Spexin peptide is expressed in human endocrine and epithelial tissues and reduced after glucose load in type 2 diabetes. Peptides. 2015;71:232–9.

    Article  CAS  PubMed  Google Scholar 

  17. Lin CY, Huang T, Zhao L, Zhong LLD, Lam WC, Fan BM, et al. Circulating spexin levels negatively correlate with age, bmi, fasting glucose, and triglycerides in healthy adult women. J Endocr Soc. 2018;2:409–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Walewski JL, Ge F, Lobdell H, Levin N, Schwartz GJ, Vasselli JR, et al. Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity. Obesity. 2014;22:1643–52.

    Article  CAS  PubMed  Google Scholar 

  19. Li S, Liu Q, Xiao L, Chen H, Li G, Zhang Y, et al. Molecular cloning and functional characterization of Spexin in orange-spotted grouper (Epinephelus coioides). Comp Biochem Physiol B Biochem Mol Biol. 2016;196-197:85–91.

    Article  CAS  PubMed  Google Scholar 

  20. Kim DK, Yun S, Son GH, Hwang JI, Park CR, Kim JI, et al. Coevolution of the Spexin/galanin/kisspeptin family: Spexin activates galanin receptor type II and III. Endocrinology. 2014;155:1864–73.

    Article  PubMed  CAS  Google Scholar 

  21. Reyes-Alcaraz A, Lee YN, Son GH, Kim NH, Kim DK, Yun S, et al. Development of Spexin-based human galanin receptor type II-Specific agonists with increased stability in serum and anxiolytic effect in mice. Sci Rep. 2016;6:21453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Reyes-Alcaraz A, Lee YN, Yun S, Hwang JI, Seong JY. Conformational signatures in beta-arrestin2 reveal natural biased agonism at a G-protein-coupled receptor. Commun Biol. 2018;1:128.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Lin CY, Zhang M, Huang T, Yang LL, Fu HB, Zhao L, et al. Spexin enhances bowel movement through activating L-type voltage-dependent calcium channel via galanin receptor 2 in mice. Sci Rep. 2015;5:12095.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lim CH, Lee MYM, Soga T, Parhar I. Evolution of structural and functional diversity of spexin in mammalian and non-mammalian vertebrate species. Front Endocrinol. 2019;10:379.

    Article  Google Scholar 

  25. Yun S, Reyes-Alcaraz A, Lee YN, Yong HJ, Choi J, Ham BJ, et al. Spexin-based galanin receptor type 2 agonist for comorbid mood disorders and abnormal body weight. Front Neurosci. 2019;13:391.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Guo L, Shi M, Zhang L, Li G, Zhang L, Shao H, et al. Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats. Gen Comp Endocrinol. 2011;173:159–63.

    Article  CAS  PubMed  Google Scholar 

  27. Porzionato A, Rucinski M, Macchi V, Stecco C, Sarasin G, Sfriso MM, et al. Spexin is expressed in the carotid body and is upregulated by postnatal hyperoxia exposure. Adv Exp Med Biol. 2012;758:207–13.

    Article  CAS  PubMed  Google Scholar 

  28. Sassek M, Kolodziejski PA, Szczepankiewicz D, Pruszynska-Oszmalek E. Spexin in the physiology of pancreatic islets-mutual interactions with insulin. Endocrine. 2019;63:513–9.

    Article  CAS  PubMed  Google Scholar 

  29. Lv SY, Zhou YC, Zhang XM, Chen WD, Wang YD. Emerging roles of NPQ/Spexin in physiology and pathology. Front Pharmacol. 2019;10:457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jeong I, Kim E, Seong JY, Park HC. Overexpression of Spexin 1 in the dorsal habenula reduces anxiety in zebrafish. Front Neural Circuits. 2019;13:53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wong MK, Sze KH, Chen T, Cho CK, Law HC, Chu IK, et al. Goldfish spexin: solution structure and novel function as a satiety factor in feeding control. Am J Physiol Endocrinol Metab. 2013;305:E348–66.

    Article  CAS  PubMed  Google Scholar 

  32. Lv S, Zhou Y, Feng Y, Zhang X, Wang X, Yang Y, et al. Peripheral Spexin inhibited food intake in mice. Int J Endocrinol. 2020;2020:4913785.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Kolodziejski PA, Pruszynska-Oszmalek E, Micker M, Skrzypski M, Wojciechowicz T, Szwarckopf P, et al. Spexin: a novel regulator of adipogenesis and fat tissue metabolism. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863:1228–36.

    Article  CAS  PubMed  Google Scholar 

  34. Pruszynska-Oszmalek E, Sassek M, Szczepankiewicz D, Nowak KW, Kolodziejski PA. Short-term administration of spexin in rats reduces obesity by affecting lipolysis and lipogenesis: An and in vitro study. Gen Comp Endocrinol. 2020;299:113615.

    Article  CAS  PubMed  Google Scholar 

  35. Zheng B, Li S, Liu Y, Li Y, Chen H, Tang H, et al. Spexin suppress food intake in zebrafish: evidence from gene knockout study. Sci Rep. 2017;7:14643.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Ma A, He M, Bai J, Wong MK, Ko WK, Wong AO. Dual role of insulin in spexin regulation: functional link between food intake and spexin expression in a fish model. Endocrinology. 2017;158:560–77.

    CAS  PubMed  Google Scholar 

  37. Wang L, Tran A, Lee J, Belsham DD. Palmitate differentially regulates Spexin, and its receptors Galr2 and Galr3, in GnRH neurons through mechanisms involving PKC, MAPKs, and TLR4. Mol Cell Endocrinol. 2020;518:110991.

    Article  CAS  PubMed  Google Scholar 

  38. Ge JF, Walewski JL, Anglade D, Berk PD. Regulation of hepatocellular fatty acid uptake in mouse models of fatty liver disease with and without functional leptin signaling: roles of NfKB and SREBP-1C and the effects of Spexin. Semin Liver Dis. 2016;36:360–72.

    Article  CAS  PubMed  Google Scholar 

  39. Gu L, Ding X, Wang Y, Gu M, Zhang J, Yan S, et al. Spexin alleviates insulin resistance and inhibits hepatic gluconeogenesis via the FoxO1/PGC-1alpha pathway in high-fat-diet-induced rats and insulin resistant cells. Int J Biol Sci. 2019;15:2815–29.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Heinonen S, Muniandy M, Buzkova J, Mardinoglu A, Rodríguez A, Frühbeck G, et al. Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity: a study of young healthy MZ twins. Diabetologia. 2017;60:169–81.

    Article  CAS  PubMed  Google Scholar 

  41. Gambaro SE, Zubiría MG, Giordano AP, Portales AE, Alzamendi A, Rumbo M, et al. “Spexin improves adipose tissue inflammation and macrophage recruitment in obese mice”. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865:158700.

    Article  CAS  PubMed  Google Scholar 

  42. Hodges SK, Teague AM, Dasari PS, Short KR. Effect of obesity and type 2 diabetes, and glucose ingestion on circulating spexin concentration in adolescents. Pediatr Diabetes. 2018;19:212–6.

    Article  CAS  PubMed  Google Scholar 

  43. Bacopoulou F, Apostolaki D, Mantzou A, Doulgeraki A, Pałasz A, Tsimaris P, et al. Serum Spexin is correlated with lipoprotein(a) and androgens in female adolescents. J Clin Med. 2019;8:12.

    Article  CAS  Google Scholar 

  44. Kumar S, Hossain J, Nader N, Aguirre R, Sriram S, Balagopal PB. Decreased circulating levels of spexin in obese children. J Clin Endocrinol Metab. 2016;101:2931–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chen T, Wang F, Chu Z, Sun L, Lv H, Zhou W, et al. Circulating spexin decreased and negatively correlated with systemic insulin sensitivity and pancreatic beta cell function in obese children. Ann Nutr Metab. 2019;74:125–31.

    Article  CAS  PubMed  Google Scholar 

  46. Behrooz M, Vaghef-Mehrabany E, Ostadrahimi A. Different spexin level in obese vs normal weight children and its relationship with obesity related risk factors. Nutr Metab Cardiovasc Dis. 2020;30:674–82.

    Article  CAS  PubMed  Google Scholar 

  47. Khadir A, Kavalakatt S, Madhu D, Devarajan S, Abubaker J, Al-Mulla F, et al. Spexin as an indicator of beneficial effects of exercise in human obesity and diabetes. Sci Rep. 2020;10:10635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lin CY, Zhao L, Huang T, Lu L, Khan M, Liu J, et al. Spexin acts as novel regulator for bile acid synthesis. Front Physiol. 2018;9:378.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kołodziejski PA, Pruszyńska-Oszmałek E, Korek E, Sassek M, Szczepankiewicz D, Kaczmarek P, et al. Serum levels of spexin and kisspeptin negatively correlate with obesity and insulin resistance in women. Physiol Res. 2018;67:45–56.

    Article  PubMed  Google Scholar 

  50. Bitarafan V, Esteghamati A, Azam K, Yosaee S, Djafarian K. Comparing serum concentration of spexin among patients with metabolic syndrome, healthy overweight/obese, and normal-weight individuals. Med J Islam Repub Iran. 2019;33:93.

    PubMed  PubMed Central  Google Scholar 

  51. Ceylan HI, Saygin O, Ozel Turkcu U. Assessment of acute aerobic exercise in the morning versus evening on asprosin, spexin, lipocalin-2, and insulin level in overweight/obese versus normal weight adult men. Chronobiol Int. 2020;37:1–17.

    Article  CAS  Google Scholar 

  52. Kumar S, Hossain MJ, Javed A, Kullo IJ, Balagopal PB. Relationship of circulating spexin with markers of cardiovascular disease: a pilot study in adolescents with obesity. Pediatr Obes. 2018;13:374–80.

    Article  CAS  PubMed  Google Scholar 

  53. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Investig. 2002;110:1093–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kumar S, Hossain MJ, Inge T, Balagopal PB. Roux-en-Y gastric bypass surgery in youth with severe obesity: 1-year longitudinal changes in spexin. Surg Obes Relat Dis. 2018;14:1537–43.

    Article  PubMed  Google Scholar 

  55. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005;352:1223–36.

    Article  CAS  PubMed  Google Scholar 

  56. Guler A, Demir I. Decreased levels of spexin are associated with hormonal and metabolic disturbance in subjects with polycystic ovary syndrome. J Obstet Gynaecol. 2020;16:1–6.

    Google Scholar 

  57. Eckel RH, Kahn SE, Ferrannini E, Goldfine AB, Nathan DM, Schwartz MW, et al. Obesity and type 2 diabetes: what can be unified and what needs to be individualized? Diabetes Care. 2011;34:1424–30.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Karaca A, Bakar-Ates F, Ersoz-Gulcelik N. Decreased Spexin levels in patients with type 1 and type 2 diabetes. Med Princ Pract. 2018;27:549–54.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Al-Daghri NM, Wani K, Yakout SM, Al-Hazmi H, Amer OE, Hussain SD, et al. Favorable changes in fasting glucose in a 6-month self-monitored lifestyle modification programme inversely affects spexin levels in females with prediabetes. Sci Rep. 2019;9:9454.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Yavuzkir S, Ugur K, Deniz R, Ustebay DU, Mirzaoglu M, Yardim M, et al. Maternal and umbilical cord blood subfatin and spexin levels in patients with gestational diabetes mellitus. Peptides. 2020;126:170277.

    Article  CAS  PubMed  Google Scholar 

  61. Akbas M, Koyuncu FM, Oludag Mete T, Taneli F, Ozdemir H, Yilmaz O. Serum levels of spexin are increased in the third trimester pregnancy with gestational diabetes mellitus. Gynecol Endocrinol. 2019;35:1050–3.

    Article  CAS  PubMed  Google Scholar 

  62. Al-Daghri NM, Al-Hazmi HA, Al-Ajlan A, Masoud MS, Al-Amro A, Al-Ghamdi A, et al. Associations of Spexin and cardiometabolic parameters among women with and without gestational diabetes mellitus. Saudi J Biol Sci. 2018;25:710–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Al-Daghri NM, Sabico S, Al-Hazmi H, Alenad AM, Al-Amro A, Al-Ghamdi A, et al. Circulating spexin levels are influenced by the presence or absence of gestational diabetes. Cytokine. 2019;113:291–5.

    Article  CAS  PubMed  Google Scholar 

  64. Ingelsson E, Sullivan LM, Fox CS, Murabito JM, Benjamin EJ, Polak JF, et al. Burden and prognostic importance of subclinical cardiovascular disease in overweight and obese individuals. Circulation. 2007;116:375–84.

    Article  PubMed  Google Scholar 

  65. Manson JE, Colditz GA, Stampfer MJ, Willett WC, Rosner B, Monson RR, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med. 1990;322:882–9.

    Article  CAS  PubMed  Google Scholar 

  66. Berenson GS, Wattigney WA, Tracy RE, Newman WP 3rd, Srinivasan SR, Webber LS, et al. Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study). Am J Cardiol. 1992;70:851–8.

    Article  CAS  PubMed  Google Scholar 

  67. Skilton MR, Celermajer DS, Cosmi E, Crispi F, Gidding SS, Raitakari OT, et al. Natural history of atherosclerosis and abdominal aortic intima-media thickness: rationale, evidence, and best practice for detection of atherosclerosis in the young. J Clin Med. 2019;8:8.

    Article  CAS  Google Scholar 

  68. Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998;338:1650–6.

    Article  CAS  PubMed  Google Scholar 

  69. McGill HC Jr., McMahan CA, Malcom GT, Oalmann MC, Strong JP. Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol. 1995;15:431–40.

    Article  PubMed  Google Scholar 

  70. Wang TJ, Wollert KC, Larson MG, Coglianese E, McCabe EL, Cheng S, et al. Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study. Circulation. 2012;126:1596–604.

    Article  CAS  PubMed  Google Scholar 

  71. The Emerging Risk Factors Collaboration C. Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet. 2011;377:1085–95.

    Article  PubMed Central  Google Scholar 

  72. Lavie CJ, Laddu D, Arena R, Ortega FB, Alpert MA, Kushner RF. Healthy weight and obesity prevention: JACC health promotion series. J Am Coll Cardiol. 2018;72:1506–31.

    Article  PubMed  Google Scholar 

  73. Group TS. Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Care. 2013;36:1758–64.

    Article  CAS  Google Scholar 

  74. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998;98:731–3.

    Article  CAS  PubMed  Google Scholar 

  75. Järvisalo MJ, Harmoinen A, Hakanen M, Paakkunainen U, Viikari J, Hartiala J, et al. Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol. 2002;22:1323–8.

    Article  PubMed  CAS  Google Scholar 

  76. Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation. 2000;102:1082–5.

    Article  CAS  PubMed  Google Scholar 

  77. Wilson PW, D’Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005;112:3066–72.

    Article  CAS  PubMed  Google Scholar 

  78. Al-Daghri NM, Alenad A, Al-Hazmi H, Amer OE, Hussain SD, Alokail MS. Spexin levels are associated with metabolic syndrome components. Dis Markers. 2018;2018:1679690.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Behrooz M, Vaghef-Mehrabany E, Moludi J, Ostadrahimi A. Are spexin levels associated with metabolic syndrome, dietary intakes and body composition in children? Diabetes Res Clin Pract. 2020;172:108634.

    Article  PubMed  CAS  Google Scholar 

  80. Liu Y, Sun L, Zheng L, Su M, Liu H, Wei Y, et al. Spexin protects cardiomyocytes from hypoxia-induced metabolic and mitochondrial dysfunction. Naunyn Schmiedebergs Arch Pharmacol. 2020;393:25–33.

    Article  CAS  PubMed  Google Scholar 

  81. Lim CH, Soga T, Levavi-Sivan B, Parhar IS. Chronic social defeat stress up-regulates spexin in the brain of Nile Tilapia (Oreochromis niloticus). Sci Rep. 2020;10:7666.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhuang M, Lai Q, Yang C, Ma Y, Fan B, Bian Z, et al. Spexin as an anxiety regulator in mouse hippocampus: Mechanisms for transcriptional regulation of spexin gene expression by corticotropin releasing factor. Biochem Biophys Res Commun. 2020;525:326–33.

    Article  CAS  PubMed  Google Scholar 

  83. Kuteeva E, Hokfelt T, Wardi T, Ogren SO. Galanin, galanin receptor subtypes and depression-like behaviour. Cell Mol Life Sci. 2008;65:1854–63.

    Article  CAS  PubMed  Google Scholar 

  84. Ogren SO, Kuteeva E, Hokfelt T, Kehr J. Galanin receptor antagonists: a potential novel pharmacological treatment for mood disorders. CNS Drugs. 2006;20:633–54.

    Article  PubMed  Google Scholar 

  85. Badie-Mahdavi H, Lu X, Behrens MM, Bartfai T. Role of galanin receptor 1 and galanin receptor 2 activation in synaptic plasticity associated with 3’,5’-cyclic AMP response element-binding protein phosphorylation in the dentate gyrus: studies with a galanin receptor 2 agonist and galanin receptor 1 knockout mice. Neuroscience. 2005;133:591–604.

    Article  CAS  PubMed  Google Scholar 

  86. Bailey KR, Pavlova MN, Rohde AD, Hohmann JG, Crawley JN. Galanin receptor subtype 2 (GalR2) null mutant mice display an anxiogenic-like phenotype specific to the elevated plus-maze. Pharmacol Biochem Behav. 2007;86:8–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sved AF, Cano G, Passerin AM, Rabin BS. The locus coeruleus, Barrington’s nucleus, and neural circuits of stress. Physiol Behav. 2002;77:737–42.

    Article  CAS  PubMed  Google Scholar 

  88. Swanson CJ, Blackburn TP, Zhang X, Zheng K, Xu ZQ, Hökfelt T, et al. Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3) antagonists SNAP 37889 and SNAP 398299. Proc Natl Acad Sci USA. 2005;102:17489–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sartorius N. Depression and diabetes. Dialogues Clin Neurosci. 2018;20:47–52.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Singh MK, Leslie SM, Packer MM, Zaiko YV, Phillips OR, Weisman EF, et al. Brain and behavioral correlates of insulin resistance in youth with depression and obesity. Horm Behav. 2019;108:73–83.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Ms. Caroline Sypniewski (University of Florida, Gainesville, FL) for her excellent help with editing the manuscript text.

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Authors and Affiliations

  1. Division of Pediatric Endocrinology, Mayo Clinic, Rochester, MN, USA

    Seema Kumar

  2. Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA

    Seema Kumar & P. Babu Balagopal

  3. Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL, USA

    Robert T. Mankowski & Stephen D. Anton

  4. Department of Biomedical Research, Nemours Children’s Health System, Jacksonville, FL, USA

    P. Babu Balagopal

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Kumar, S., Mankowski, R.T., Anton, S.D. et al. Novel insights on the role of spexin as a biomarker of obesity and related cardiometabolic disease. Int J Obes 45, 2169–2178 (2021). https://doi.org/10.1038/s41366-021-00906-2

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