Evaluation of serum irisin levels in patients with endometrial hyperplasia: A controlled cross-sectional study

Yıl 2019, , 242 - 245, 15.03.2019

Erdem Şahin , Mefküre Eraslan Şahin , Yusuf Madendağ , İlknur Çöl Madendağ , Ahter Tanay Tayyar , Murat Gözüküçük Ciğdem Karakükçü , Gökhan Açmaz

https://doi.org/10.28982/josam.536426

Öz

Aim: Irisin, which is proteolytically splited form of fibronectin type III domain containing 5 (FNDC5), is a protein with 112 amino acid. Irisin is an exercise-induced hormone excreted primarily by cardiac muscle and skeletal cells which can be described as an exercise hormone and a new potential target for the treatment of metabolic diseases and obesity. Our goal was to evaluate the serum irisin levels in patients with endometrial hyperplasia (EH). 

Methods: An observational study is planned. The study population consisted of two groups: 1) the EH group (study group), consisting of participants who had been histopathologically diagnosed with simple EH without atypia and 2) the control group, consisting of healthy participants admitted to the clinic for an annual examination without any complaints or symptoms. Primary outcome of the study was evaluation irisin status. Serum irisin levels were determined by an enzyme-linked immunosorbent assay (ELISA) method.

Results: After sample size analysis, 52 participants enrolled into the study as study group (EH group) (n=26) and control group (n=26). The mean age was 39.5±3.8 years in the EH group and 40.7±2.4 years in the control group (p=0.258). Mean BMI was 28.8±2.1 kg/m2 in the EH group and 28.5±1.2 kg/m2 in the control group (p=0.666). Gravidity, parity, systolic blood pleasure, diastolic blood pleasure, fasting glucose levels, smoking status, alcohol use were similar for both groups (p=0.499, p=0.278, p=0.248, p=0.424, p=0.646, p=0.486 and p=0.153, respectively). In control group regular exercise rates was significantly higher than EH group (26.9%, 3.84%, respectively p<0.001). The mean serum irisin level was 1.9±0.7 μg/ml in the EH group and 3.5±2.0 μg/ml in the control group. Serum irisin levels were found to be significantly lower in the EH group compared to the control group (p<0.001). 

Conclusion: The data from the current study indicate that serum irisin levels were significantly decreased in patients with endometrial hyperplasia. Serum irisin levels may open up new horizons for therapeutic targets for the treatment of patients with EH.

Anahtar Kelimeler

Endometrial hyperplasia, Obesity, Sedentary life, Physical activity, Irisin

Endometrial hiperplazili hastalarda serum irisin düzeylerinin değerlendirilmesi: Kontrollü kesitsel çalışma

Öz

Amaç: Proteolitik olarak bölünmüş 5 (FNDC5) içeren fibronektin tip III alan formunda olan irisin, 112 amino asitli bir proteindir. İrisin, temel olarak kalp kası ve iskelet hücreleri tarafından salgılanan, egzersiz hormonu ve metabolik hastalıkların ve obezitenin tedavisi için yeni bir potansiyel hedef olarak tanımlanabilen, egzersiz kaynaklı bir hormondur. Amacımız endometrial hiperplazi (EH) hastalarında serum irisin düzeylerini değerlendirmektir.

Yöntemler: Çalışma popülasyonu iki gruptan oluşmaktadır: 1) histopatolojik olarak atipisiz basit EH tanısı almış EH grubu ve 2) kliniğe herhangi bir yakınması ve şikayeti olmadan yıllık muayene için başvuran kontrol grubu. Çalışmanın primer sonucu serum irisin seviyelerinin araştırılmasıdır. Serum irisin düzeyleri, enzyme-linked immunosorbent assay (ELISA) yöntemiyle belirlendi.

Bulgular. Örneklem büyüklüğü analizi sonrası toplam 52 katılımcı çalışmaya dahil edildi (EH grubu (n=26) ve kontrol grubu (n=26)). Ortalama yaş EH grubunda 39,5±3,8, kontrol grubunda 40,7±2,4 idi (p=0,262). EH grubunda ortalama VKI 28,8±2,1 kg/m2, kontrol grubunda 28,5±1,2 kg/m2 idi (p=0,666). Gravidite, parite, sistolik kan basıncı, diyastolik kan basıncı, açlık glikoz seviyeleri, sigara içme durumu, alkol kullanımı her iki grup için benzerdi (sırasıyla p=0.499, p=0.278, p=0.248, p=0.424, p=0.646, p=0.486 ve p=0.153). Kontrol grubunda düzenli egzersiz oranları EH grubundan anlamlı olarak yüksekti (sırasıyla %26,9, %3,84, p<0,001). Ortalama serum irisin düzeyi EH grubunda 1,9±0,7 μg/ml ve kontrol grubunda 3,5±2,0 μg/ml idi. Serum irisin düzeyleri EH grubunda kontrol grubuna gore anlamlı olarak düşük bulundu (p<0.001).

Sonuç. Mevcut çalışmadan elde edilen veriler, endometrial hiperplazili hastalarda serum irisin düzeylerinin anlamlı derecede azaldığını göstermektedir. Serum irisin düzeyleri, EH'li hastaların tedavisinde terapötik hedefler için yeni ufuklar açabilir.

Anahtar Kelimeler

Endometrial hiperplazi, Obesite, Sedanter yaşam, Fiziksel aktivite, İrisin

Kaynakça

• 1. Sahin E, Eraslan Sahin M, Dolanbay M, et al. Induction of apoptosis by metformin and progesterone in estrogen-induced endometrial hyperplasia in rats: involvement of the bcl-2 family proteins. Gynecol Endocrinol. 2018 May;34(5):433-6.
• 2. Daud S, Jalil SS, Griffin M, et al. Endometrial hyperplasia - the dilemma of management remains: a retrospective observational study of 280 women. Eur J Obstet Gynecol Reprod Biol. 2011 Nov;159(1):172-5. doi: 10.1016/j.ejogrb.2011.06.023. PubMed PMID: 21764501.
• 3. Beavis AL, Smith AJ, Fader AN. Lifestyle changes and the risk of developing endometrial and ovarian cancers: opportunities for prevention and management. Int J Womens Health. 2016;8:151-67. doi: 10.2147/IJWH.S88367. PubMed PMID: 27284267; PubMed Central PMCID: PMCPMC4883806.
• 4. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004 Jan;84(1):277-359. doi: 10.1152/physrev.00015.2003. PubMed PMID: 14715917.
• 5. Gannon NP, Vaughan RA, Garcia-Smith R, et al. Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro. Int J Cancer. 2015 Feb 15;136(4):E197-202. doi: 10.1002/ijc.29142. PubMed PMID: 25124080.
• 6. Provatopoulou X, Georgiou GP, Kalogera E, et al. Serum irisin levels are lower in patients with breast cancer: association with disease diagnosis and tumor characteristics. BMC Cancer. 2015 Nov 11;15:898. doi: 10.1186/s12885-015-1898-1. PubMed PMID: 26560078; PubMed Central PMCID: PMCPMC4642638.
• 7. Moon HS, Mantzoros CS. Regulation of cell proliferation and malignant potential by irisin in endometrial, colon, thyroid and esophageal cancer cell lines. Metabolism. 2014 Feb;63(2):188-93. doi: 10.1016/j.metabol.2013.10.005. PubMed PMID: 24268368.
• 8. Blizzard LeBlanc DR, Rioux BV, Pelech C, et al. Exercise‐induced irisin release as a determinant of the metabolic response to exercise training in obese youth: the EXIT trial. Physiological reports. 2017;5(23).
• 9. Aydin S, Aydin S, Kuloglu T, et al. Alterations of irisin concentrations in saliva and serum of obese and normal-weight subjects, before and after 45 min of a Turkish bath or running. Peptides. 2013 Dec;50:13-8. doi: 10.1016/j.peptides.2013.09.011. PubMed PMID: 24096106.
• 10. Winn NC, Grunewald ZI, Liu Y, et al. Plasma Irisin Modestly Increases during Moderate and High-Intensity Afternoon Exercise in Obese Females. PLoS One. 2017;12(1):e0170690. doi: 10.1371/journal.pone.0170690. PubMed PMID: 28125733; PubMed Central PMCID: PMCPMC5268488.
• 11. Kerr J, Anderson C, Lippman SM. Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. Lancet Oncol. 2017 Aug;18(8):e457-e471. doi: 10.1016/S1470-2045(17)30411-4. PubMed PMID: 28759385.
• 12. Ballard-Barbash R, Friedenreich CM, Courneya KS, et al. Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst. 2012 Jun 6;104(11):815-40. doi: 10.1093/jnci/djs207. PubMed PMID: 22570317; PubMed Central PMCID: PMCPMC3465697.
• 13. Hibler E. Epigenetics and Colorectal Neoplasia: the Evidence for Physical Activity and Sedentary Behavior. Curr Colorectal Cancer Rep. 2015 Dec;11(6):388-396. doi: 10.1007/s11888-015-0296-z. PubMed PMID: 27212896; PubMed Central PMCID: PMCPMC4869522.
• 14. Robinson MM, Dasari S, Konopka AR, et al. Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans. Cell Metab. 2017 Mar 7;25(3):581-592. doi: 10.1016/j.cmet.2017.02.009. PubMed PMID: 28273480; PubMed Central PMCID: PMCPMC5423095.
• 15. Wiseman AJ, Lynch BM, Cameron AJ, et al. Associations of change in television viewing time with biomarkers of postmenopausal breast cancer risk: the Australian Diabetes, Obesity and Lifestyle Study. Cancer Causes Control. 2014 Oct;25(10):1309-19. doi: 10.1007/s10552-014-0433-z. PubMed PMID: 25053405.
• 16. Lynch BM, Dunstan DW, Healy GN, et al. Objectively measured physical activity and sedentary time of breast cancer survivors, and associations with adiposity: findings from NHANES (2003-2006). Cancer Causes Control. 2010 Feb;21(2):283-8. doi: 10.1007/s10552-009-9460-6. PubMed PMID: 19882359.
• 17. Borch KB, Weiderpass E, Braaten T, et al. Physical activity and risk of endometrial cancer in the Norwegian Women and Cancer (NOWAC) study. Int J Cancer. 2017 Apr 15;140(8):1809-1818. doi: 10.1002/ijc.30610. PubMed PMID: 28108996.
• 18. Schmid D, Leitzmann MF. Television viewing and time spent sedentary in relation to cancer risk: a meta-analysis. J Natl Cancer Inst. 2014 Jul;106(7). doi: 10.1093/jnci/dju098. PubMed PMID: 24935969.
• 19. Biswas A, Oh PI, Faulkner GE, et al. Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis. Ann Intern Med. 2015 Jan 20;162(2):123-32. doi: 10.7326/M14-1651. PubMed PMID: 25599350.
• 20. Shen D, Mao W, Liu T, et al. Sedentary behavior and incident cancer: a meta-analysis of prospective studies. PLoS One. 2014;9(8):e105709. doi: 10.1371/journal.pone.0105709. PubMed PMID: 25153314; PubMed Central PMCID: PMCPMC4143275.
• 21. Linkov F, Edwards R, Balk J, et al. Endometrial hyperplasia, endometrial cancer and prevention: gaps in existing research of modifiable risk factors. Eur J Cancer. 2008 Aug;44(12):1632-44. doi: 10.1016/j.ejca.2008.05.001. PubMed PMID: 18514507.
• 22. Polyzos SA, Anastasilakis AD, Efstathiadou ZA, et al. Irisin in metabolic diseases. Endocrine. 2018;59(2):260-74.
• 23. Jang HB, Kim HJ, Kang JH, et al. Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents. Metabolism. 2017 Aug;73:100-108. doi: 10.1016/j.metabol.2017.05.007. PubMed PMID: 28732566.
• 24. Bastu E, Zeybek U, Gurel Gurevin E, et al. Effects of Irisin and Exercise on Metabolic Parameters and Reproductive Hormone Levels in High-Fat Diet-Induced Obese Female Mice. Reprod Sci. 2018 Feb;25(2):281-91. doi: 10.1177/1933719117711264. PubMed PMID: 28594316.
• 25. Ural UM, Sahin SB, Tekin YB, et al. Alteration of maternal serum irisin levels in gestational diabetes mellitus. Ginekol Pol. 2016;87(5):395-8. doi: 10.5603/GP.2016.0013. PubMed PMID: 27304658.
• 26. Huh JY. The role of exercise-induced myokines in regulating metabolism. Arch Pharm Res. 2018 Jan;41(1):14-29. doi: 10.1007/s12272-017-0994-y. PubMed PMID: 29177585.
• 27. Shoukry A, Shalaby SM, El-Arabi Bdeer S, et al. Circulating serum irisin levels in obesity and type 2 diabetes mellitus. IUBMB Life. 2016 Jul;68(7):544-56. doi: 10.1002/iub.1511. PubMed PMID: 27220658.