Iranian Journal of Medical Sciences

Document Type : Original Article(s)


1 Department of Molecular and Medical Biotechnology, College of Biotechnology, Al-Nahrain University, Baghdad,Iraq

2 Department of Chemistry, College of Science, Al-Nahrain University, Jadriya, Baghdad, Iraq

3 Department of Chemistry, Faculty of Education, Thamar University, Thamar, Yemen



Background: A combination of genetic and environmental factors contribute to the highly common, complex, and varied endocrine condition known as polycystic ovary syndrome (PCOS) in women. PCOS primarily affects women between the ages of 15 and 35 who are in the early to late stages of pregnancy.  Thus, this study aimed to evaluate the serum levels of irisin, subfatin, and adropin in PCOS with and without obesity compared to the control group.
Methods: The present cross-sectional study was conducted in 2022 at Al-Nahrain University/Department of Chemistry (Baghdad, Iraq). The serum levels of irisin, subfatin, and adropin were measured with the enzyme-linked immunosorbent assay (ELISA) method. Body mass index, lipid profile, insulin, fasting glucose, follicle-stimulating hormone, and luteinizing hormone levels were also evaluated. The data were analyzed using one-way analysis of variance (ANOVA) by GraphPad Prism software version 8.0.2. A P<0.05 was considered statistically significant.
Results: The study population comprised PCOS patients (n=90, divided into 45 obese and 45 normal weight) and healthy women (n=30). According to the results, the serum levels of irisin were significantly higher (P<0.001) in obese and normal-weight PCOS patients than controls. While adropin and subfatin were significantly lower in PCOS than controls (P<0.001). Moreover, there are higher levels of serum insulin, fasting glucose, and luteinizing hormone in PCOS women than in healthy women.
Conclusion: According to the findings, PCOS patients had a higher level of irisin than the controls. In addition, decreased subfatin and adropin levels were observed in PCOS patients compared with healthy women. Further research is required to confirm these results in the future.


  1. Forslund M, Landin-Wilhelmsen K, Trimpou P, Schmidt J, Brannstrom M, Dahlgren E. Type 2 diabetes mellitus in women with polycystic ovary syndrome during a 24-year period: importance of obesity and abdominal fat distribution. Hum Reprod Open. 2020;2020:hoz042. doi: 10.1093/hropen/hoz042. PubMed PMID: 31976382; PubMed Central PMCID: PMCPMC6964225.
  2. Huang J, Liu L, Chen C, Gao Y. PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels. BMC Endocr Disord. 2020;20:3. doi: 10.1186/s12902-019-0486-9. PubMed PMID: 31906930; PubMed Central PMCID: PMCPMC6945624.
  3. Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15:6184-223. doi: 10.3390/ijms15046184. PubMed PMID: 24733068; PubMed Central PMCID: PMCPMC4013623.
  4. Reyes-Farias M, Fos-Domenech J, Serra D, Herrero L, Sanchez-Infantes D. White adipose tissue dysfunction in obesity and aging. Biochem Pharmacol. 2021;192:114723. doi: 10.1016/j.bcp.2021.114723. PubMed PMID: 34364887.
  5. Ushach I, Burkhardt AM, Martinez C, Hevezi PA, Gerber PA, Buhren BA, et al. METEORIN-LIKE is a cytokine associated with barrier tissues and alternatively activated macrophages. Clin Immunol. 2015;156:119-27. doi: 10.1016/j.clim.2014.11.006. PubMed PMID: 25486603; PubMed Central PMCID: PMCPMC4336607.
  6. Du Y, Ye X, Lu A, Zhao D, Liu J, Cheng J, et al. Inverse relationship between serum Metrnl levels and visceral fat obesity (VFO) in patients with type 2 diabetes. Diabetes Res Clin Pract. 2020;161:108068. doi: 10.1016/j.diabres.2020.108068. PubMed PMID: 32044349.
  7. Islam MR, Valaris S, Young MF, Haley EB, Luo R, Bond SF, et al. Exercise hormone irisin is a critical regulator of cognitive function. Nat Metab. 2021;3:1058-70. doi: 10.1038/s42255-021-00438-z. PubMed PMID: 34417591; PubMed Central PMCID: PMCPMC10317538.
  8. Erickson HP. Irisin and FNDC5 in retrospect: An exercise hormone or a transmembrane receptor? Adipocyte. 2013;2:289-93. doi: 10.4161/adip.26082. PubMed PMID: 24052909; PubMed Central PMCID: PMCPMC3774709.
  9. Aydin S, Kuloglu T, Aydin S, Kalayci M, Yilmaz M, Cakmak T, et al. A comprehensive immunohistochemical examination of the distribution of the fat-burning protein irisin in biological tissues. Peptides. 2014;61:130-6. doi: 10.1016/j.peptides.2014.09.014. PubMed PMID: 25261800.
  10. Brnic D, Martinovic D, Zivkovic PM, Tokic D, Tadin Hadjina I, Rusic D, et al. Serum adropin levels are reduced in patients with inflammatory bowel diseases. Sci Rep. 2020;10:9264. doi: 10.1038/s41598-020-66254-9. PubMed PMID: 32518265; PubMed Central PMCID: PMCPMC7283308.
  11. Gao S, McMillan RP, Zhu Q, Lopaschuk GD, Hulver MW, Butler AA. Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance. Mol Metab. 2015;4:310-24. doi: 10.1016/j.molmet.2015.01.005. PubMed PMID: 25830094; PubMed Central PMCID: PMCPMC4354928.
  12. Christ JP, Cedars MI. Current Guidelines for Diagnosing PCOS. Diagnostics (Basel). 2023;13. doi: 10.3390/diagnostics13061113. PubMed PMID: 36980421; PubMed Central PMCID: PMCPMC10047373.
  13. Farhan FS, Hussien SS. Irisin as a Novel Marker for Insulin Resistance in Iraqi Women with Polycystic Ovary Syndrome Before and After Metformin Therapy. J Obstet Gynaecol India. 2019;69:194-200. doi: 10.1007/s13224-018-1176-7. PubMed PMID: 31686756; PubMed Central PMCID: PMCPMC6801237.
  14. Aydin E, Ozkokeli M. Does homeostasis model assessment of insulin resistance have a predictive value for post-coronary artery bypass grafting surgery outcomes? Rev Bras Cir Cardiovasc. 2014;29:360-6. doi: 10.5935/1678-9741.20140105. PubMed PMID: 25372910; PubMed Central PMCID: PMCPMC4412326.
  15. Onat T, Inandiklioglu N, Kara M, Serdar Yalvac E, Turkler C, Ciplak B, et al. Increased serum myonectin and irisin levels with myonectin and FNDC5 expressions in polycystic ovary syndrome: a case control study. J Obstet Gynaecol. 2022;42:1381-7. doi: 10.1080/01443615.2021.1980516. PubMed PMID: 34907845.
  16. Ashour WM, Abdel-Aleem D, Khalil SS, Elkazzaz OM. Serum adropin and vaspin levels in obese rats with polycystic ovary syndrome and after metformin treatment. Zagazig University Medical Journal. 2021;27:193-202.
  17. Zhu B, Wang B, Zhao C, Wang Y, Zhou Y, Lin J, et al. Irisin Regulates Cardiac Responses to Exercise in Health and Diseases: a Narrative Review. J Cardiovasc Transl Res. 2023;16:430-42. doi: 10.1007/s12265-022-10310-4. PubMed PMID: 36036861.
  18. Li M, Yang M, Zhou X, Fang X, Hu W, Zhu W, et al. Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015;100:1485-93. doi: 10.1210/jc.2014-2544. PubMed PMID: 25675380.
  19. Li H, Xu X, Wang X, Liao X, Li L, Yang G, et al. Free androgen index and Irisin in polycystic ovary syndrome. J Endocrinol Invest. 2016;39:549-56. doi: 10.1007/s40618-015-0403-7. PubMed PMID: 26584566.
  20. Chang CL, Huang SY, Soong YK, Cheng PJ, Wang CJ, Liang IT. Circulating irisin and glucose-dependent insulinotropic peptide are associated with the development of polycystic ovary syndrome. J Clin Endocrinol Metab. 2014;99:E2539-48. doi: 10.1210/jc.2014-1180. PubMed PMID: 25029417.
  21. Zhang L, Fang X, Li L, Liu R, Zhang C, Liu H, et al. The association between circulating irisin levels and different phenotypes of polycystic ovary syndrome. J Endocrinol Invest. 2018;41:1401-7. doi: 10.1007/s40618-018-0902-4. PubMed PMID: 29785700.
  22. Pukajlo K, Laczmanski L, Kolackov K, Kuliczkowska-Plaksej J, Bolanowski M, Milewicz A, et al. Irisin plasma concentration in PCOS and healthy subjects is related to body fat content and android fat distribution. Gynecol Endocrinol. 2015;31:907-11. doi: 10.3109/09513590.2015.1065482. PubMed PMID: 26172924.
  23. Wang W, Guo Y, Zhang X, Zheng J. Abnormal irisin level in serum and endometrium is associated with metabolic dysfunction in polycystic ovary syndrome patients. Clin Endocrinol (Oxf). 2018;89:474-80. doi: 10.1111/cen.13805. PubMed PMID: 29972694.
  24. Crujeiras AB, Pardo M, Casanueva FF. Irisin: ‘fat’ or artefact. Clin Endocrinol (Oxf). 2015;82:467-74. doi: 10.1111/cen.12627. PubMed PMID: 25287317.
  25. Garces MF, Peralta JJ, Ruiz-Linares CE, Lozano AR, Poveda NE, Torres-Sierra AL, et al. Irisin levels during pregnancy and changes associated with the development of preeclampsia. J Clin Endocrinol Metab. 2014;99:2113-9. doi: 10.1210/jc.2013-4127. PubMed PMID: 24628554.
  26. Park KH, Zaichenko L, Brinkoetter M, Thakkar B, Sahin-Efe A, Joung KE, et al. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab. 2013;98:4899-907. doi: 10.1210/jc.2013-2373. PubMed PMID: 24057291; PubMed Central PMCID: PMCPMC3849667.
  27. Zhang L, Wu X, Li X, Chang X, Ding X, Wang Q, et al. Longitudinal changes in serum adropin levels and liver fat content during liraglutide treatment in newly diagnosed patients with type 2 diabetes mellitus and metabolic dysfunction-associated fatty liver disease. Acta Diabetol. 2023;60:971-9. doi: 10.1007/s00592-023-02082-3. PubMed PMID: 37079136; PubMed Central PMCID: PMCPMC10198855.
  28. Ke Y, Hu J, Zhu Y, Wang Y, Chen S, Liu S. Correlation Between Circulating Adropin Levels and Patients with PCOS: An Updated Systematic Review and Meta-analysis. Reprod Sci. 2022;29:3295-310. doi: 10.1007/s43032-022-00841-1. PubMed PMID: 35015289.
  29. Inal ZO, Erdem S, Gederet Y, Duran C, Kucukaydin Z, Kurku H, et al. The impact of serum adropin and ischemia modified albumin levels based on BMI in PCOS. Endokrynol Pol. 2018;69:135-41. doi: 10.5603/EP.a2018.0002. PubMed PMID: 29465156.
  30. Varikasuvu SR, Reddy EP, Thangappazham B, Varshney S, Das VL, Munikumar M. Adropin levels and its associations as a fat-burning hormone in patients with polycystic ovary syndrome: a correlational meta-analysis. Gynecol Endocrinol. 2021;37:879-84. doi: 10.1080/09513590.2021.1950136. PubMed PMID: 34241553.
  31. Kuliczkowska-Plaksej J, Mierzwicka A, Jonczyk M, Stachowska B, Urbanovych A, Bolanowski M. Adropin in women with polycystic ovary syndrome. Endokrynol Pol. 2019;70:151-6. doi: 10.5603/EP.a2018.0092. PubMed PMID: 30480749.
  32. Bousmpoula A, Kouskouni E, Benidis E, Demeridou S, Kapeta-Kourkouli R, Chasiakou A, et al. Adropin levels in women with polycystic ovaries undergoing ovarian stimulation: correlation with lipoprotein lipid profiles. Gynecol Endocrinol. 2018;34:153-6. doi: 10.1080/09513590.2017.1379498. PubMed PMID: 28937295.
  33. Wyse BA, Salehi R, Russell SJ, Sangaralingam M, Jahangiri S, Tsang BK, et al. Obesity and PCOS radically alters the snRNA composition of follicular fluid extracellular vesicles. Front Endocrinol (Lausanne). 2023;14:1205385. doi: 10.3389/fendo.2023.1205385. PubMed PMID: 37404312; PubMed Central PMCID: PMCPMC10315679.
  34. Ye Z, Zhang C, Zhao Y. Potential effects of adropin on systemic metabolic and hormonal abnormalities in polycystic ovary syndrome. Reprod Biomed Online. 2021;42:1007-14. doi: 10.1016/j.rbmo.2021.01.020. PubMed PMID: 33612434.
  35. Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell. 2014;157:1279-91. doi: 10.1016/j.cell.2014.03.065. PubMed PMID: 24906147; PubMed Central PMCID: PMCPMC4131287.
  36. Fouani FZ, Fadaei R, Moradi N, Zandieh Z, Ansaripour S, Yekaninejad MS, et al. Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study. PLoS One. 2020;15:e0231943. doi: 10.1371/journal.pone.0231943. PubMed PMID: 32330176; PubMed Central PMCID: PMCPMC7182262.
  37. Li ZY, Zheng SL, Wang P, Xu TY, Guan YF, Zhang YJ, et al. Subfatin is a novel adipokine and unlike Meteorin in adipose and brain expression. CNS Neurosci Ther. 2014;20:344-54. doi: 10.1111/cns.12219. PubMed PMID: 24393292; PubMed Central PMCID: PMCPMC6492994.
  38. Deniz R, Yavuzkir S, Ugur K, Ustebay DU, Baykus Y, Ustebay S, et al. Subfatin and asprosin, two new metabolic players of polycystic ovary syndrome. J Obstet Gynaecol. 2021;41:279-84. doi: 10.1080/01443615.2020.1758926. PubMed PMID: 32608281.
  39. Lee JH, Kang YE, Kim JM, Choung S, Joung KH, Kim HJ, et al. Serum Meteorin-like protein levels decreased in patients newly diagnosed with type 2 diabetes. Diabetes Res Clin Pract. 2018;135:7-10. doi: 10.1016/j.diabres.2017.10.005. PubMed PMID: 29097285.
  40. Schmid A, Karrasch T, Schaffler A. Meteorin-Like Protein (Metrnl) in Obesity, during Weight Loss and in Adipocyte Differentiation. J Clin Med. 2021;10. doi: 10.3390/jcm10194338. PubMed PMID: 34640356; PubMed Central PMCID: PMCPMC8509786.
  41. El-Ashmawy HM, Selim FO, Hosny TAM, Almassry HN. Association of low serum Meteorin like (Metrnl) concentrations with worsening of glucose tolerance, impaired endothelial function and atherosclerosis. Diabetes Res Clin Pract. 2019;150:57-63. doi: 10.1016/j.diabres.2019.02.026. PubMed PMID: 30825562.
  42. Chung HS, Hwang SY, Choi JH, Lee HJ, Kim NH, Yoo HJ, et al. Implications of circulating Meteorin-like (Metrnl) level in human subjects with type 2 diabetes. Diabetes Res Clin Pract. 2018;136:100-7. doi: 10.1016/j.diabres.2017.11.031. PubMed PMID: 29199003.