The evaluation of serum Adropin and Lipocalin levels in women with polycystic ovary syndrome

Abstract

Purpose: Polycystic Ovary Syndrome (PCOS) is related to metabolic diseases such as endothelial dysfunction, systemic inflammation, insülin resistance and dyslipidemia. Adropin is a peptide secretion that positively affects glucose homeostasis and hepatic steatosis in patients with PCOS. Lipocalin-2 mediates obesity, insulin resistance, and apoptosis induced by IL-3. The levels of adropin and lipocalin-2 in PCOS patients were studied in this study.
Materials and methods: Women with PCOS (n=37) and healthy controls (n=34) were assessed in this observational and cross-sectional study. Anthropometric measurements, demographic data, metabolic and hormonal profiles, Adropin and Lipocalin-2 levels were measured in both groups.
Results: In the study it was determined that PCOS group Adropin and Lipocalin-2 levels were significantly reduced. LDL-C cholesterol, Total cholesterol, Total testosterone, LH, FAI, Triglyceride and LH/FSH values and hirsutism score considerably lower in the control group than the PCOS group.
Conclusion: The fact that adropin levels were reduced significantly in PCOS patients who had not yet acquired insulin resistance or who could not be detected using existing methods suggests that adropin changes in PCOS are independent of insulin. The study shows that the level of adropin decreases significantly before insulin resistance reaches pathological levels, which is associated with the young population. Low Lipocalin-2 levels in patients with PCOS suggest that this cannot be blamed for insulin receptor dysfunction secondary to apoptosis in PCOS.

Keywords

• Adropin
• lipocalin
• insulin
• polycystic ovary syndrome

Project Number

1904

Polikistik over sendrom tanılı hastalarda Adropin ve Lipokalin düzeylerinin incelenmesi

Abstract

Amaç: Polikistik Over Sendromu (PKOS) metabolik bozukluklarla ilişkilidir. Bunlar özellikle endotel disfonksiyonu, insülin direnci, sistemik inflamasyon ve dislipidemi olarak belirtilmiştir. PKOS’lu hastalarda glikoz homeostazı ve hepatik steatozu olumlu bir biçimde etkileyen peptit yapılı bir salgı ‘adropin’ olarak adlandırılır. Lipokalin-2 apoptoziste aracı rolü üstlenmekte ve IL-3, obezite, insülin direnci tarafından uyarılmaktadır. Bu araştırmada PKOS’lu hastalarda adropin ve lipokalin-2 seviyeleri araştırılmıştır.
Gereç ve yöntem: Bu gözlemsel ve kesitsel çalışmada hastalar 18-38 yaş aralığında PKOS tanısı almış (n=37) ve sağlıklı kadın kontrol grubu (n=34) olarak sınıflandırıldı. Her iki grupta demografik veriler, metabolik ve hormonal değerler, antropometrik ölçümler, serum Lipokalin-2 ve Adropin seviyeleri ölçüldü.
Bulgular: Araştırmada PKOS’lu hasta grubunda Lipokalin-2 ve Adropin düzeylerindeki düşüşün anlamlı olduğu bulunmuştur. Kontrol grubunda LDL-C kolesterol, Total kolesterol, Total testosteron, LH, FAI, Trigliserit ve LH/FSH değerleri ve hirsutizm skoru PKOS grubuna göre daha düşük seviyelerde saptanmıştır.
Sonuç: Adropinin PKOS’ta insülinden bağımsız olarak farklılaşması PKOS’lu hastalarda insülin direnci tespiti ve gelişimi ortaya konulmadan adropin düzeylerindeki anlamlı azalma sonucu ortaya konulmaktadır. Çalışma insülin direncinin patolojik seviyelere gelmeden adropin düzeyinin anlamlı olarak azaldığını ve bu durumun popülasyonun genç olması ile ilişkili olduğunu göstermektedir. PKOS’da apoptozise ikincil insülin reseptör fonksiyon bozukluğunun Lipokalin-2 seviyeleri ile ilişkili olmadığı ve bunun nedeninin PKOS’lu hastalarda Lipokalin-2 seviyelerinin düşük olmasından kaynaklandığı vurgulanmaktadır. 

Keywords

• Adropin
• lipokalin
• insulin
• polikistik over sendromu

Supporting Institution

Pamukkale Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Project Number

1904

References

1. 1. Fauser BC, Tarlatzis BC, Rebar RW, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28-38.e25. doi:10.1016/j.fertnstert.2011.09.024
2. 2. Bhide P, Homburg R. Anti-Müllerian hormone and polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2016 Nov;37:38-45. doi: 10.1016/j.bpobgyn.2016.03.004. Epub 2016 Apr 1. PMID: 27103234.
3. 3. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016 Dec;31(12):2841-2855. doi: 10.1093/humrep/dew218. Epub 2016 Sep 22. PMID: 27664216.
4. 4. Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012 Oct;27(10):3067-73. doi: 10.1093/humrep/des232. Epub 2012 Jul 9. PMID: 22777527.
5. 5. Bellver J, Rodríguez-Tabernero L, Robles A, et al. Polycystic ovary syndrome throughout a woman's life. J Assist Reprod Genet. 2018;35(1):25-39. doi:10.1007/s10815-017-1047-7
6. 6. Kshetrimayum C, Sharma A, Mishra VV, Kumar S. Polycystic ovarian syndrome: Environmental/occupational, lifestyle factors; an overview. J Turk Ger Gynecol Assoc. 2019 Nov 28;20(4):255-263. doi: 10.4274/jtgga.galenos.2019.2018.0142. Epub 2019 Mar 1. PMID: 30821135; PMCID: PMC6883751.
7. 7. Marczuk N, Cecerska-Heryć E, Jesionowska A, Dołęgowska B. Adropin - physiological and pathophysiological role. Postepy Hig Med Dosw (Online). 2016 Sep 26;70(0):981-988. doi: 10.5604/17322693.1220082. PMID: 27668650.
8. 8. 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 Jan 17;4(4):310-24. doi: 10.1016/j.molmet.2015.01.005. PMID: 25830094; PMCID: PMC4354928.

9. 9. Kumar KG, Trevaskis JL, Lam DD, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008;8(6):468-481. doi:10.1016/j.cmet.2008.10.011
10. 10. Aydin S, Kuloglu T, Aydin S. Copeptin, adropin and irisin concentrations in breast milk and plasma of healthy women and those with gestational diabetes mellitus. Peptides. 2013 Sep;47:66-70. doi: 10.1016/j.peptides.2013.07.001. Epub 2013 Jul 9. PMID: 23850897.
11. 11. Wang Y, Lam KS, Kraegen EW, et al. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem. 2007;53(1):34-41. doi:10.1373/clinchem.2006.075614
12. 12. Mosialou I, Shikhel S, Liu JM, et al. MC4R-dependent suppression of appetite by bone-derived lipocalin 2 [published correction appears in Nature. 2017 Jun 14;546(7658):440]. Nature. 2017;543(7645):385-390. doi:10.1038/nature21697
13. 13. Panidis D, Tziomalos K, Koiou E, et al. The effects of obesity and polycystic ovary syndrome on serum lipocalin-2 levels: a cross-sectional study. Reprod Biol Endocrinol. 2010;8:151. Published 2010 Dec 9. doi:10.1186/1477-7827-8-151
14. 14. Esteve E, Ricart W, Fernández-Real JM. Adipocytokines and insulin resistance: the possible role of lipocalin-2, retinol binding protein-4, and adiponectin. Diabetes Care. 2009 Nov;32 Suppl 2(Suppl 2):S362-7. doi: 10.2337/dc09-S340. PMID: 19875582; PMCID: PMC2811453.
15. 15. Gencer M, Gazi E, Hacıvelioğlu S, et al. The relationship between subclinical cardiovascular disease and lipocalin-2 levels in women with PCOS. Eur J Obstet Gynecol Reprod Biol. 2014;181:99-103. doi:10.1016/j.ejogrb.2014.07.032
16. 16. Koiou E, Tziomalos K, Katsikis I, et al. Weight loss significantly reduces serum lipocalin-2 levels in overweight and obese women with polycystic ovary syndrome. Gynecol Endocrinol. 2012;28(1):20-24. doi:10.3109/09513590.2011.588745
17. 17. Cakal E, Ozkaya M, Engin-Ustun Y, Ustun Y. Serum lipocalin-2 as an insulin resistance marker in patients with polycystic ovary syndrome. J Endocrinol Invest. 2011 Feb;34(2):97-100. doi: 10.1007/BF03347037. Epub 2010 May 28. PMID: 20511727.
18. 18. Hu L, Shen H, Wu QF, Tian L, Hu MH. Treatment of polycystic ovarian syndrome with insulin resistance by insulin-sensitizer. Clin Exp Obstet Gynecol. 2014;41(3):288-92. PMID: 24992778.
19. 19. 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. PMID: 24992783.
20. 20. Kume T, Calan M, Yilmaz O, et al. A possible connection between tumor necrosis factor alpha and adropin levels in polycystic ovary syndrome. J Endocrinol Invest. 2016;39(7):747-754. doi:10.1007/s40618-016-0453-5
21. 21. Inal ZO, Erdem S, Gederet Y, et al. The impact of serum adropin and ischemia modified albumin levels based on BMI in PCOS. Endokrynol Pol. 2018;69(2):135-141. doi:10.5603/EP.a2018.0002
22. 22. Sen H, Erbag G, Bınnetoglu E, et al. Adropin levels in polycystic ovary syndrome patients. J Clin Anal Med. 2017; 8(1)
23. 23. Kuliczkowska-Płaksej J, Mierzwicka A, Jończyk M, Stachowska B, Urbanovych A, Bolanowski M. Adropin in women with polycystic ovary syndrome. Endokrynol Pol. 2019;70(2):151-156. doi:10.5603/EP.a2018.0092
24. 24. Hamdi RA, Abas HN, Alsaeed FAA. Role of Adropin in Women with Polycystic Ovary Syndrome. Scopus Ijphrd Cıtatıon Score 2019;10(9): 291.
25. 25. Diamanti-Kandarakis E, Livadas S, Kandarakis SA, Margeli A, Papassotiriou I. Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: hint of a protective mechanism?. Eur J Endocrinol. 2008;158(4):525-531. doi:10.1530/EJE-07-0822
26. 26. Yilmaz Ö, Temur M, Calan M, et al. The relationship between lipocalin-2 and free testosterone levels in polycystic ovary syndrome. Endokrynol Pol. 2017;68(1):7-12. doi:10.5603/EP.2017.0002