HORMONE ADROPINE: ITS EFFECT ON AGE-ASSOCIATED DISEASES

DOI: https://doi.org/10.29296/24999490-2021-02-03

B.I. Kuznik(1, 2), N.I. Chalisova(3, 4) 1-Chita State Medical Academy, Gorkogo str. 39a, Chita, 672090, Russian Federation; 2-Clinic of the Academy of Health Innovation, Kokhanskogo str., 13, Chita, 672000, Russian Federation; 3-Pavlov Institute of Physiology RAS, nab. Makarova, 6, St. Petersburg, 199034, Russian Federation; 4-St. Petersburg Institute of Bioregulation and Gerontology, pr. Dinamo, 3, St. Petersburg, 197110, Russian Federation E-mail: ni_chalisova@mail.ru

The purpose of the review was the search and analysis of the data about hormone adropin, similar to the known hormone irisin, and its effect on the pathology, associated with aging. Adropin is expressed in many following organs as referred to CNS, in liver, kidney, heart, pancreas, jejunum, in endothelial cells, milk, foremilk. The effect of adropin is related to the regulation of energetic balance, glucose, and fatty acid metabolism. The adropin concentration is decreased with the age but is increased by the physical loading. Adropin plays a great role in CNS function and its concentration is decreased in blood and brain by the neurodegenerative diseases. Experiments in animals demonstrated, that adropin can decrease the degenerative symptoms in CNS. The adropin concentration in blood is decreased by the pathology of the cardiovascular system, by diabetes melitus, metabolic syndrome, cancer of mammary gland, and endometrium. A negative correlation is detected between the adropin concentration and arterial pressure, endothelin concentration and insulin resistance, and positive correlation between cardial troponin and natrium-uretic peptide. Adropin is beleived to play a great role in the development of pathology, associated with aging.
Keywords: 
adropin, irisin, CNS, cardiovascular system, diabetes mellitus, metabolic syndrome, oncology pathology, aging

Список литературы: 
  1. Bostrom P., Wu J., Jedrychowski, M.P., Korde A., Ye L., Lo J.C., Rasbach, K.A., Bostrom, E.A., Choi J.H., Long J.Z., Kajimura S., Zingaretti M.C., Vind B.F., Tu H., Cinti S., Hojlund K., Gygi S.P., Spiegelman B.M. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 7382: 463–8.
  2. Joung K.E., Park, K.H., Filippaios A., Dincer F., Christou H., Mantzoros C.S. Cord blood irisin levels are positively correlated with birth weight in newborn infants. Metabolism. 2015; 64 (11): 1507–14.
  3. Kumar K.G, Trevaskis J.L., Lam D.D., Sutton G.M., Koza R.A., Chouljenko V.N., Kousoulas K.G., Rogers P.M., Kesterson R.A., Thearle M., Ferrante A.W. Jr. Mynatt R.L, Burris T.P., Dong J.Z., Halem H.A., Culler M.D., Heisler L.K., Stephens J.M., Butler A.A. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008; 8 (6): 468–81.
  4. Aydin S. Three new players in energy regulation: preptin, adropin and irisin. Peptides. 2014; 56: 94–110.
  5. Kuznik B.I. Havinson V.H., Davydov S.O., Stepanov A.V. Belki molodosti i starosti. Belki – markery kletochnogo starenija i predskazateli prodolzhitel'nosti zhizni. Palmarium, academic publishing. 2017; 285. [Kuznik B.I. Havinson V.H., Davydov S.O., Stepanov A.V. Proteins of youth and old age. Proteins-markers of cellular aging and predictors of life expectancy. Palmarium, academic publishing. 2017; 285 (in Russian)]
  6. Havinson V.H., Kuznik B.I., Ryzhak G.A., Lin'kova N.S., Sall' T.S., Chalisova N.I. Irisin, betatrofin, saharnyj diabet, ozhirenie i metabolicheskij sindrom. Epigeneticheskie mehanizmy reguljatsi. Uspehi fiziologicheskih nauk. 2018; 49 (1): 72–86. [Khavinson V.Kh., Kuznik B.I., Ryzhak G.A., Linkova N.S., Sall T.S., Chalisova N.I. Irisin, betatrophin, diabetes, obesity and metabolic syndrome. Epygenetic regulatory mechanisms. Uspekhi Fiziologicheskikh Nauk. 2018; 49 (1): 72–86 (in Russian)]
  7. Kuznik B.I., Davydov S.O., Chalisova N.I. Rol' belkov MANF, TIMP-2 I IRISINA v starenii organizma. Uspehi sovremennoj biologii. 2019; 139 (6): 540–51. [Kuznik B.I., Davidov S.O., Chalisova N.I. MANF, TIMP-2 and Irisin effect in organism aging. Uspekhi Sovremennoi Biologii. 2019; 139 (6): 540–51 (in Russian)]
  8. Kuznik B.I., Davydov S.O., Stepanov A.V. Rol' myshechnogo gormona irisina v reguljatsii fiziologicheskih funktsij v uslovijah normy i patologii. Uspehi fiziologicheskih nauk. 2018; 49 (4): 59–80. [Kuznik B.I., Davidov S.O., Stepanov S.O. Role of muscle hormone Irisin in regulation of physiological functions at norm and pathology. Uspekhi Fiziologicheskikh Nauk. 2018; 49 (4): 59–80 (in Russian)]
  9. Marczuk N., Cecerska-Heryć E., Jesionowska A., Dołęgowska B. Adropin – physiological and pathophysiological role. Postepy Hig. Med. Dosw. (Online). 2016; 70 (9): 981–8.
  10. Butler A.A., Tam C.S., Stanhope K.L., Wolfe B.M., Ali M.R., O’Keeffe M., St-Onge M.P., Ravussin E., Havel P.J. Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans. J. Clin. Endocrinol. Metab. 2012; 97 (10): 3783–91. DOI: 10.1210/jc.2012-2194.
  11. Yang C., De Mars K.M., Candelario-Jalil E. Age-Dependent Decrease in Adropin is Associated with Reduced Levels of Endothelial Nitric Oxide Synthas and Increased Oxidative Stress in the Rat Brain. Aging Dis. 2018; 9 (2): 322–30. DOI: 10.14336/AD.2017.0523.
  12. Kwon O.S., Andtbacka R.H.I., Hyngstrom J.R., Richardson R.S. Vasodilatory function in human skeletal muscle feed arteries with advancing age: the role of adropin. J. Physiol. 2019; 597 (7): 1791–804. DOI: 10.1113/JP277410.
  13. Zhang H., Jiang L., Yang Y.J., Ge R.K., Zhou M., Hu H., Liu H., Cui J., Li L.L., Dong Y.F., Cheng X.S., Chen R., Li P. Aerobic exercise improves endothelial function and serum adropin levels in obese adolescents independent of body weight loss. Sci. Rep. 2017; 7 (1): 17717.
  14. Fujie S., Hasegawa N., Sato K., Fujita S., Sanada K., Hamaoka T., Iemitsu M. Aerobic exercise training-induced changes in serum adropin level are associated with reduced arterial stiffness in middle-aged and older adults. Am. J. Physiol. Heart Cir. c Physiol. 2015; 309 (10): 1642–7. DOI: 10.1152/ajpheart.00338.2015.
  15. Soori R., Amini A.A., Choobineh S., Eskandari A., Behjat A., Ghram A., Voltarelli F.A. Exercise attenuates myocardial fibrosis and increases angiogenesis-related molecules in the myocardium of aged rats. Arch. Physiol. Biochem. 2019; 2: 1–6.
  16. Yang C., DeMars K.M., Candelario-Jalil E. Age-Dependent Decrease in Adropin is Associated with Reduced Levels of Endothelial Nitric Oxide Synthase and Increased Oxidative Stress in the Rat Brain. Aging Dis. 2018; 9 (2): 322–30. DOI: 10.14336/AD.2017.0523.
  17. Wong C.M., Wang Y., Lee J.T., Huang Z., Wu D., Xu A. Adropin is a brain membrane-bound protein regulating physical activity via the NB-3/Notch signaling pathway in mice. J. Biol. Chem. 2014; 289: 25976–86.
  18. Stein L.M., Yosten G.L.C., Samson W.K. Adropin acts in brain to inhibit water drinking: potential interaction with the orphan G protein-coupled receptor, GPR19. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2016; 310: 476–80. DOI: 10.1152/ajpregu.00511.2015.
  19. Hossain M.S., Mineno K., Katafuchi T. Neuronal orphan g-protein coupled receptor proteins mediate plasmalogens-induced activation of ERK and Akt signaling. PLoS ONE. 2016; 11: e0150846. DOI: 10.1371/journal.pone.0150846.
  20. Shahjouei S., Ansari S., Pourmotabbed T., Zand R. Potential Roles of Adropin in Central Nervous System: Review of Current Literature Front. Mol. Biosci. 2016; 3: 25–8.
  21. Loewen S.P., Ferguson A.V. Adropin acts in the rat paraventricular nucleus to influence neuronal excitability. Am. J. Physiol Regul Integr Comp Physiol. 2017; 312: 511–9.
  22. Gao S., Mcmillan R.P., Zhu Q., Lopaschuk G.D., Hulver M.W., Butler A.A. Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet- induced obese mice with insulin resistance. Mol. Metab. 2015; 4: 1–15. DOI: 10.1016/j.molmet.2015.01.005.
  23. Hernandez-Guillamon M., Martinez-Saez E., Delgado P., Domingues-Montanari S., Boada C., Penalba A., et al. MMP-2/MMP-9 plasma level and brain expression in cerebral amyloid angiopathy-associated hemorrhagic stroke. Brain Pathol. 2012; 22: 133–41. DOI: 10.1111/j.1750-3639.2011.00512.
  24. Ueno M., Chiba Y., Matsumoto K., Murakami R., Fujihara R., Kawauchi M., Blood-brain barrier damage in vascular dementia. Neuropathology. 2016; 36: 115–24. DOI: 10.1111/neup.12262.
  25. Lovren F., Pan Y., Quan A., Singh K. K., Shukla P. C., Gupta M. Adropin is a novel regulator of endothelial function. Circulation. 2010; 122: 185–92. DOI: 10.1161/CIRCULATION 109.931782.
  26. Bolayir H.A., Kivrak Tarik , Gunes Hakan , Bolayir Asl. Adropin and circadian variation of blood pressure.Kardiol Pol. 2018; 76 (4): 776–82. PMID 29313563.
  27. Sato K., Yamashita T, Shirai R., Shibata K., Okano T., Yamaguchi M., Mori Y, Hirano T., Watanabe T. Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation. J. Mol. Sci. 2018; 19 (5): 1293–7.
  28. Aydin S., Kuloglu T., Aydin S., Kalayci M., Yilmaz M., Ҫakmak T., Eren M.N. Elevated adropin: a candidate diagnostic marker for myocardial infarction in conjunction with troponin-I. Peptides. 2014; 58: 91–7.
  29. Yu H.Y., Zhao P., Wu M.C., Liu J., Yin W. Serum adropin levels are decreased in patients with acute myocardial infarction. Regul. Pept. 2014; 190–191: 46–9.
  30. Zhang C., Zhao L., Xu W., Li J., Wang B., Gu X., Chen. J.: Correlation of serum adropin level with coronary artery disease. Zhonghua Yi Xue Za Zhi. 2014; 94: 1255–7.
  31. Ertem A.G., Sefa Ünal, Tolga Han Efe , Burak Açar , Çağri Yayla , Mevlüt Serdar Kuyumcu , Association between serum adropin level and burden of coronary artery disease in patients with non-ST elevation myocardial infarction. Anatol. J. Cardiol. 2017; 17 (2): 119–24. PMID 27684517.
  32. Gu X. , Hui Li, Xinyi Zhu, Haibo Gu, Jianchang Chen, Luchen Wang, Pamela Harding, Weiting Xu. Inverse Correlation Between Plasma Adropin and ET-1 Levels in Essential Hypertension: A Cross-Sectional Study.Medicine (Baltimore). 2015; 94 (40): e1712. Clinical Trial. PMID 26448026.
  33. Lin D., Jian Yong , Shuhua Ni , Weichao Ou, Xuerui TanJian Yong. Negative association between serum adropin and hypertensive disorders complicating pregnancy. Hypertens. Pregnancy. 2019; 38 (4): 237–44. PMID 31438729.
  34. Wang B., Xue Y., Shang F., Ni S., Liu X., Fan B., Wang H.. Association of serum adropin with the presence of atrial fibrillation and atrial remodeling. .J. Clin. Lab. Anal. 2019; 33 (2): e22672.
  35. Kalkan A.K. , Huseyin Altug Cakmak , Mehmet Erturk , Kübra Erol Kalkan , Fatih Uzun , Omer Tasbulak , Vesile Ornek Diker , Suleyman Aydin Ahmet Celik Adropin and Irisin in Patients With Cardiac Cachexia. Arq. Bras. Cardiol. 2018; 111 (1): 39–47.
  36. Kałużna M., Krzysztof Pawlaczyk, Krzysztof Schwermer, Krzysztof Hoppe, Magdalena Człapka-Matyasik, Adropin and irisin: New biomarkers of cardiac status in patients with end-stage renal disease? A preliminary study. Adv. Clin. Exp. Med. 2019; 28 (3): 347–53.
  37. Aydin S., Kuloglu T., Aydin S., Eren M.N., Yilmaz M., Kalayci M., Sahin I., Kocaman N., Citil C., Kendir Y. Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes. Mol. Cell. Biochem. 2013; 380: 73–81. DOI: 10.1007/s11010-013-1660-4.
  38. Kuloglu T., Aydin S. Immunohistochemical expressions of adropin and inducible nitric oxide synthase in renal tissues of rats with streptozotocin-induced experimental diabetes. Biotech. Histochem. 2014; 89: 104–10. DOI: 10.3109/10520295.2013.821713.
  39. Akcilar R., Kocak F.E., Simsek H., Akcilar A., Bayat Z., Ece E., Kokdasgil H. Antidiabetic and hypolipidemic effects of adropinin streoptozotocin-induced type 2 diabetic rats. Bratislavske Lekarske Listy. 2016; 117: 100–5. DOI: 10.4149/BLL.
  40. Gao S., Ghoshal S., Zhang L., Stevens J.R., McCommis K.S., Finck B.N., Lopaschuk G.D., Butler A.A. The peptide hormone adropin regulates signal transduction pathways controlling hepatic glucose metabolism in a mouse model of diet-induced obesity. J. Biol. Chem. 2019; 294: 13366–77. DOI: 10.1074/jbc.RA119.008967.
  41. Butler A.A., Zhang J., Price C.A., Stevens J.R., Graham J.L., Stanhope K.L., King S., Krauss R.M., Bremer A.A., Havel P.J. Low plasma adropin concentrations increase risks of weight gain and metabolic dysregulation in response to a high-sugar diet in male nonhuman primates. Biol Chem. 2019; 294 (25): 9706–19. DOI: 10.1074/jbc.RA119.007528.
  42. Chen S., Zeng K., Liu Q., Guo Z., Zhang S., Chen X.R., Lin J.H., Wen J.P., Zhao C.F., Lin X.H. F. Adropin deficiency worsens HFD-induced metabolic effect. Cell Death Dis. 2017; 8 (8): e3008. DOI: 10.1038/cddis.2017.362.
  43. Wu L., Fang J., Chen L., Zhao Z., Luo Y., Lin C., Fan L. Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic and non-diabetic patients. Clin. Chem. Lab. Med. 2014; 52: 751–8. DOI: 10.1515/cclm-2013-0844
  44. Li S., Sun J., Hu W., Liu Y., Lin D., Duan H., Liu F. The association of serum and vitreous adropin concentrations with diabetic retinopathy. Ann. Clin. Biochem. 2019; 56 (2):253-8. doi: 10.1177/0004563218820359.
  45. Polkowska A., Pasierowska I.E., Paslawska M., Pawluczuk E., Bossowski A. Assessment of Serum Concentrations of Adropin, Afamin, and Neudesin in Children with Type 1 Diabetes. BioMed. Res. Internat. 2019; 6128410. DOI: 10.1155/2019/6128410.
  46. Thapa D., Xie B., Manning J.R., Zhang M., Stoner M.W., Huckestein B.R., Edmunds L.R., Zhang X., Dedousis N.L., O’Doherty R.M. Adropin reduces blood glucose levels in mice by limiting hepatic glucose production. Physiol. Rep. 2019; 7: e14043.
  47. Beigi Aboutaleb, Nooshin Shirzad , Fatemeh Nikpour , Ensieh Nasli Esfahani , Solaleh Emamgholipour , Fatemeh Bandarian. Association Between Serum Adropin Levels and Gestational Diabetes Mellitus. A Case-Control Study. Gynecol. Endocrinol. 2015; 31 (12): 939–41.
  48. Celik E., Yilmaz E., Celik O., Ulas M., Turkcuoglu I., Karaer A., Simsek Y., Minareci Y., Aydin S.J. Perinatal maternal and fetal adropin levels in gestational diabetes mellitus. Med. 2013; 41 (4): 375–80. DOI: 10.1515/jpm-2012-0227.
  49. Jasaszwili M., Billert M., Strowski M.Z., Nowak K.W., Skrzypski M. Adropin as A Fat-Burning Hormone with Multiple Functions-Review of a Decade of Research. Molecules. 2020; 25 (3): 549–53. DOI: 10.3390/molecules25030549
  50. Palizban A.A., Yazdani A.H., Jahanbani-Ardakani H. Role of rs7903146 polymorphism and adropin serum level in patients with diabetes mellitus; a case-control study from Isfahan, Iran. Arch. Physiol. Biochem. 2019; 9: 1–4. DOI: 10.1080/13813455.2019.1684951
  51. Aydin S., Kuloglu T. Copeptin, Adropin and Irisin Concentrations in Breast Milk and Plasma of Healthy Women and Those With Gestational Diabetes Mellitus. Peptides. 2013; 47: 66–70.
  52. Choi H.N., Yim J.E.J. Plasma Adropin as a Potential Marker Predicting Obesity and Obesity-associated Cancer in Korean Patients With Type 2 Diabetes Mellitus. Cancer Prev. 2018; 23 (4): 191–6. DOI: 10.15430/JCP.2018.23.4.191.
  53. Butler A.A., Tam C.S., Stanhope K.L., Wolfe B.M., Ali M.R., O’Keeffe M., St-Onge M.P., Ravussin E., Havel P.J. Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans. J. Clin. Endocrinol. Metab. 2012; 97 (10): 3783–91. DOI: 10.1210/jc.2012-2194.
  54. Yosaee S., Khodadost M., Esteghamati A., Speakman J.R., Shidfar F., Nazari M.N., Bitarafan V., Djafarian K..Am. Metabolic Syndrome Patients Have Lower Levels of Adropin When Compared With Healthy Overweight/Obese and Lean Subjects J. Mens Health. 2017; 11 (2): 426–34. DOI: 10.1177/1557988316664074..
  55. Korkmaz S., Sayilan Özgün, Turk G. Serum adropin levels in psoriasis vulgaris and its relation with metabolic parameters. J. Med. Sci. 2019; 49 (1): 110–5. DOI: 10.3906/sag-1712-192
  56. Dogan S., Rogozina O.P., Lokshin A.E., Grande J.P., Cleary M.P. Effects of chronic vs. intermittent calorie restriction on mammary tumor incidence and serum adiponectin and leptin levels in MMTV-TGF-alpha mice at different ages. Oncol. Lett. 2010; 1 (1): 167–76.
  57. Tuna B.G., Atalay P.B., Altunbek M., Kalkan B.M., Dogan S. Effects of Chronic and Intermittent Calorie Restriction on Adropin Levels in Breast Cancer. Nutr. Cancer. 2017; 69 (7): 1003–10. DOI: 10.1080/01635581.2017.1359314.
  58. Nergiz S., Altinkaya S.O., Kurt Ömürlü İ., Yuksel H., Küçük M., Demircan Sezer S. Circulating adropin levels in patients with endometrium cancer. Gynecol. Endocrinol. 2015; 31 (9): 730–5. DOI: 10.3109/09513590.2015.1065480.
  59. Kume T., Calan M., Yilmaz O., Kocabas G.U., Yesil P., Temur M., Bicer M., Calan O.G. A possible connection between tumor necrosis factor alpha and adropin levels in polycystic ovary syndrome. J. Endocrinol. Invest. 2016; 39 (7): 747–54. DOI: 10.1007/s40618-016-0453-5.
  60. Yildirim B., Celik O., Aydin S. Adropin: a key component and potential gatekeeper of metabolic disturbances in policystic ovarian syndrome. Clin. Exp. Obstet. Gynecol. 2014; 41 (3): 310–2.
  61. Encarnacion M.R., Beata B.M., Kenneth D. Causes, consequences, and reversal of immune system aging. The J. of Clinical Investigation. 2013; 123 (3): 958–65. DOI: 10.1172/JCI64096