The Role of Chemerin In Polycystic Over Syndrome

Yıl 2021, , 197 - 210, 31.08.2021

Fatmanur Hümeyra Zengin , Efsun Karabudak

https://doi.org/10.47115/jshs.752616

Öz

Polycystic ovarian syndrome (PCOS) is a heterogeneous disease defined by a combination of androgen excess and ovarian dysfunction. Although the etiology of PCOS is not fully known, hyperandrogenism, obesity, dyslipidemia, chronic inflammation and insulin resistance have a significant impact on the development of the syndrome. Adipose tissue, especially white adipose tissue, is under the influence of sex steroids, this effect is versatile and complex. Adipose tissue is prone to hypertrophy when exposed to androgen excess, and both adipose tissue hypertrophy and hyperandrogenism are associated with insulin resistance. Chronic low-grade inflammation caused by adipose tissue disorder has also been shown to play a role in the development of metabolic and reproductive disorders of PCOS. Chemerin, recently joined the adipokine family as a new chemoattractant protein. Chemerin has been shown in studies to play an important role in differentiation of human adipocytes, inflammation, glucose and lipid metabolism. It is thought that chemerin may contribute to the development of PCOS by associating it with insulin resistance and its inflammatory role as a chemoattractant substance in adipose tissue. In recent studies, serum chemerin concentrations have been found significantly higher in PCOS patients compared to healthy individuals and chemerin has been associated with body mass index, blood lipids, insulin resistance and hyperandrogenism. Understanding the underlying mechanisms will help to better understand the pathology of PCOS and identify the new therapeutic goals of this syndrome. This review will focus on the possible effect of chemerin on the pathophysiology of PCOS.

Anahtar Kelimeler

PCOS, Chemerin, Adipose tissue, Insulin resistance, Inflammation

POLİKİSTİK OVER SENDROMUNDA CHEMERİNİN ROLÜ

Öz

Polikistik over sendromu (PKOS), androjen fazlalığının (klinik veya biyokimyasal) ve over disfonksiyonunun (oligo-ovulasyon ve / veya polikistik over morfolojisi ) kombinasyonu ile tanımlanan heterojen bir hastalıktır. Polikistik over sendromunun etiyolojisi tam olarak bilinmemesine rağmen hiperandrojenizm, obezite (özellikle abdominal obezite), dislipidemi, kronik inflamasyon ve insülin direnci sendromun gelişiminde önemli bir etkiye sahiptir. Adipoz doku, özellikle beyaz adipoz doku, cinsiyet steroidlerinin etkisi altındadır, bu etki çok yönlü ve karmaşıktır. Adipoz doku androjen fazlalığına maruz kaldığında hipertrofiye eğilimlidir ve hem adipoz doku hipertrofisi hem de hiperandrojenizm, insülin direnciyle ilişkilidir. Adipoz doku bozukluğunun neden olduğu kronik düşük dereceli inflamasyonun da PKOS'un metabolik ve üreme bozukluklarının gelişiminde rol oynayabileceği gösterilmiştir. Büyük oranda beyaz adipoz dokudan salgılanan chemerin, yakın zamanda yeni bir kemoatraktan protein olarak adipokin ailesine katılmıştır. Chemerinin insan adipositlerinin farklılaşmasında, inflamasyon, glukoz ve lipit metabolizmasında önemli bir rol oynadığı çalışmalarda gösterilmiştir. Chemerinin, obezite ve insülin direnci ile ilişkilendirilmesi ayrıca adipoz dokuda kemoatraktan bir madde olarak inflamatuvar rolü sayesinde PKOS gelişimine katkıda bulunabileceği düşünülmektedir. Son yıllarda yapılan çalışmalarda PKOS’lu bireylerde serum chemerin konsantrasyonları sağlıklı bireylerle karşılaştırıldığında anlamlı olarak yüksek bulunmuş ve chemerin; beden kütle indeksi (BKİ), kan lipitleri, insülin direnci ve hiperandrojenizm ile ilişkilendirilmiştir. Altta yatan mekanizmaların anlaşılması PKOS patolojisini daha iyi anlamaya ve bu sendromun yeni terapötik hedeflerini tanımlamaya yardımcı olacaktır. Bu derlemede, PKOS patofizyolojisinde chemerinin olası etkileri üzerinde durulacaktır.

Anahtar Kelimeler

PKOS, adipoz doku, insülin direnci, inflamasyon, Chemerin

Kaynakça

• Kaynaklar Adrenal ve Gonadal Hastalıklar Çalışma Grubu. (2018). Adrenal ve Gonadal Hastalıklar Kılavuzu. Miki Matbaacılık San. Ltd. Şti. Ankara. Erişim adresi: http://www.temd.org.tr/admin/uploads/tbl_gruplar/20180517113623-2018-05 17tbl_gruplar113620.pdf Erişim tarihi: 10.03.2020. Aydoğdu, A,, Haymana, C., Tapan, S., Taşlıpınar, A., Yazıcı, M., Başaran, Y., Dinç, M., Sönmez, A., Azal, Ö. (2015). Polikistik over sendromu olgularında artmış visseral adipozite indeksi; inflamasyon, insülin direnci ve hiperandrojenite arasındaki ilişki. Gülhane Tıp Derg, 57(2), 107-110. Azziz, R. (2018). Polycystic Ovary Syndrome. Obstet Gynecol., 132(2), 321–336. doi:10.1097/AOG.0000000000002698 Azziz, R., Carmina, E., Dewailly, D., Diamanti-Kandarakis, E., Escobar-Morreale, H.F., Futterweit, W, ve diğ. (2006). Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab, 91, 4237–4245. Blagojević, I.P., Ignjatović, S., Macut, D., Kotur-Stevuljević, J., Božić-Antić, I., Vekić, J. ve diğ. (2018). Evaluation of a Summary Score for Dyslipidemia, Oxidative Stress and Inflammation (the Doi Score) in Women with Polycystic Ovary Syndrome and its Relationship with Obesity. J Med Biochem., 37(4), 476–485. doi:10.2478/jomb-2018-00 Bódis, K., Roden, M. (2018). Energy metabolism of white adipose tissue and insulin resistance in humans. Eur J Clin Invest., 48(11), e13017. doi:10.1111/eci.13017 Bongrani, A., Mellouk, N., Rame, C., Cornuau, M., Guérif, F., Froment, P. ve diğ. (2019). Ovarian Expression of Adipokines in Polycystic Ovary Syndrome: A Role for Chemerin, Omentin, and Apelin in Follicular Growth Arrest and Ovulatory Dysfunction?. Int J Mol Sci., 20(15), E3778. doi: 10.3390/ijms20153778. Booth, A., Magnuson, A., Fouts, J., Foster, M.T. (2016). Adipose tissue: an endocrine organ playing a role in metabolic regulation. Horm Mol Biol Clin Investig., 26(1), 25–42. doi:10.1515/hmbci-2015-0073 Bozaoglu, K., Bolton, K., McMillan, J., Zimmet, P., Jowett, J., Collier, G. ve diğ. (2007). Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology., 148(10), 4687–4694. doi:10.1210/en.2007-0175 Bozdag, G., Mumusoglu, S., Zengin, D., Karabulut, E., Yildiz, B.O. (2016). The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Human Reproduction, 31(12), 2841-55. Brutocao, C., Zaiem, F., Alsawas, M., Morrow, A.S., Murad, M.H., Javed, A. (2018). Psychiatric disorders in women with polycystic ovary syndrome: a systematic review and meta-analysis. Endocrine., 62(2), 318-325. doi: 10.1007/s12020-018-1692-3 Buechler, C., Feder, S., Haberl, E.M., Aslanidis, C. (2019). Chemerin Isoforms and Activity in Obesity. Int J Mol Sci., 20(5), 1128. doi:10.3390/ijms20051128 Chen, X., Jia, X., Qiao, J., Guan, Y., Kang, J. (2013). Adipokines in reproductive function: a link between obesity and polycystic ovary syndrome. J Mol Endocrinol., 50(2), R21–R37..doi:10.1530/JME-12-0247. Cooke, P.S., Heine, P.A., Taylor, J.A., Lubahn, D.B. (2001). The role of estrogen and estrogen receptor-alpha in male adipose tissue. Mol Cell Endocrinol., 178(1-2), 147–154. doi:10.1016/s0303-7207(01)00414-2 Doğan, Ş.B., Ballı, U., Dede, F.Ö., Sertoğlu, E., Tazegül. K. (2016). Chemerin as a Novel Crevicular Fluid Marker of Patients With Periodontitis and Type 2 Diabetes Mellitus. J Periodontol., 87(8), 923–933. doi:10.1902/jop.2016.150657 Douglas. C.C., Gower. B.A., Darnell, B.E., Ovalle, F., Oster, R.A., Azziz, R. (2006). Role of diet in the treatment of polycystic ovary syndrome. Fertil Steril., 85(3), 679-88. Escobar-Morreale, H.F. (2018). Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol., 14(5), 270–284. doi:10.1038/nrendo.2018.24 Estienne, A., Bongrani, A., Reverchon, M., Ramé, C., Ducluzeau, P.H., Froment, P. ve diğ. (2019). Involvement of Novel Adipokines, Chemerin, Visfatin, Resistin and Apelin in Reproductive Functions in Normal and Pathological Conditions in Humans and Animal Models. Int J Mol Sci., 20(18), E4431. doi: 10.3390/ijms20184431. Fatima, S.S., Rehman, R., Baig, M., Khan, T.A. (2014). New roles of the multidimensional adipokine: chemerin. Peptides., 62, 15–20. doi:10.1016/j.peptides.2014.09.019 Foda, A.A., Foda, E.A., El-Negeri, M.A., El-Said, Z.H. (2019). Serum chemerin levels in Polycystic Ovary Syndrome after metformin therapy. Diabetes Metab Syndr., 13(2), 1309–1315. doi:10.1016/j.dsx.2019.01.050 Goralski, K.B., McCarthy, T.C., Hanniman, E.A., Zabel, B.A., Butcher, E.C., Parlee, S.D. ve diğ. (2007). Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem., 282(38); 28175-88. Guvenc, Y., Var, A., Goker, A., Kuscu, N.K. (2016). Assessment of serum chemerin, vaspin and omentin-1 levels in patients with polycystic ovary syndrome. J Int Med Res., 44(4), 796–805. doi:10.1177/0300060516645421. Guzel, E.C., Celik, C., Abali, R., Kucukyalcin, V., Celik, E., Guzel, M. ve diğ. (2014). Omentin and chemerin and their association with obesity in women with polycystic ovary syndrome. Gynecol Endocrinol., 30(6), 419–422. doi:10.3109/09513590.2014.888412 Huang, R., Yue, J., Sun, Y., Zheng, J., Tao, T., Li, S. ve diğ. (2015). Increased serum chemerin concentrations in patients with polycystic ovary syndrome: Relationship between insulin resistance and ovarian volume. Clin Chim Acta., 450, 366-9. doi: 10.1016/j.cca.2015.09.015 Hauner, H. (2005). Secretory factors from human adipose tissue and their functional role. Proc Nutr Soc., 64(2), 163–169. doi:10.1079/pns2005428. Huang, X., Fu, C., Liu, W., Liang, Y., Li, P., Liu, Z. ve diğ. (2019). Chemerin-induced angiogenesis and adipogenesis in 3 T3-L1 preadipocytes is mediated by lncRNA Meg3 through regulating Dickkopf-3 by sponging miR-217. Toxicol Appl Pharmacol., 385, 114815. doi:10.1016/j.taap.2019.114815 Ibáñez, L., Jaramillo, A.M., Ferrer, A., de Zegher, F. (2005). High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception. Hum Reprod., 20(9), 2457–2462. doi:10.1093/humrep/dei072 Jacewicz-Święcka, M., Kowalska, I. (2018). Polycystic ovary syndrome and the risk of cardiometabolic complications in longitudinal studies. Diabetes Metab Res Rev., 34(8), e3054. doi: 10.1002/dmrr.3054. Kakoly, N.S., Khomami, M.B., Joham, A.E., Cooray, S.D., Misso, M.L., Norman, R.J., Harrison, C.L., Ranasinha, S., Teede, H.J., Moran, L.J. (2018). Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression. Hum Reprod Update., 24(4), 455-467. doi: 10.1093/humupd/dmy007. Kim, J.Y., Xue, K., Cao, M., Wang, Q., Liu, J.Y., Leader, A. ve diğ. (2013). Chemerin suppresses ovarian follicular development and its potential involvement in follicular arrest in rats treated chronically with dihydrotestosterone. Endocrinology., 154(8), 2912–2923. doi:10.1210/en.2013-1001. Kort, D.H., Kostolias, A., Sullivan, C., Lobo, R.A. (2015). Chemerin as a marker of body fat and insulin resistance in women with polycystic ovary syndrome. Gynecol Endocrinol., 31(2), 152–155. doi:10.3109/09513590.2014.968547 Li, L., Feng, Q., Ye, M., He, Y., Yao, A., Shi, K. (2017). Metabolic effect of obesity on polycystic ovary syndrome in adolescents: a meta-analysis. J Obstet Gynaecol., 37(8), 1036–1047. doi:10.1080/01443615.2017.1318840 Lim, S.S., Hutchison, S.K., Van, Ryswyk.E., Norman, R.J., Teede, H.J., Moran, L.J. (2019) Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev., 3, CD007506. doi: 10.1002/14651858.CD007506.pub4.a Lim, S.S., Kakoly, N.S., Tan, J.W.J., Fitzgerald, G., Bahri, Khomami, M., Joham, A.E. ve diğ. (2019). Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression. Obes Rev., 20(2), 339-352. doi: 10.1111/obr.12762.b Lima, P.D.A., Nivet, A.L., Wang, Q., Chen, Y.A., Leader, A. ve diğ. (2018). Polycystic ovary syndrome: possible involvement of androgen-induced, chemerin-mediated ovarian recruitment of monocytes/macrophages. Biol Reprod., 99(4), 838–852. doi: 10.1093/biolre/ioy096 Mathew, H., Castracane, V.D., Mantzoros, C. (2018). Adipose tissue and reproductive health. Metabolism., 86, 18–32. doi:10.1016/j.metabol.2017.11.006 Mu, L., Li, R., Lai, Y., Zhao, Y., Qiao, J. (2019). Adipose insulin resistance is associated with cardiovascular risk factors in polycystic ovary syndrome. J Endocrinol Invest., (5), 541-548. doi: 10.1007/s40618-018-0949-2.ü Nagpal, S., Patel, S., Jacobe, H., DiSepio, D., Ghosn, C., Malhotra, M. ve diğ. (1997). Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin. J Invest Dermatol., 109(1), 91–95. doi:10.1111/1523-1747.ep12276660 Newell-Fugate, A.E. (2017). The role of sex steroids in white adipose tissue adipocyte function. Reproduction., 153(4), R133–R149. doi:10.1530/REP-16-0417 Niklowitz, P., Rothermel, J., Lass, N., Barth, A., Reinehr, T. (2018). Link between chemerin, central obesity, and parameters of the Metabolic Syndrome: findings from a longitudinal study in obese children participating in a lifestyle intervention. Int J Obes (Lond)., 42(10), 1743–1752. doi:10.1038/s41366-018-0157-3). Raucci, R., Rusolo, F., Sharma, A., Colonna, G., Castello, G., Costantini, S. (2013). Functional and structural features of adipokine family. Cytokine., 61(1), 1-14. doi: 10.1016/j.cyto.2012.08.036. Reverchon, M., Cornuau, M., Rame, C., Guerif, F., Royère, D., Dupont, J. (2012). Chemerin inhibits IGF-1- induced progesterone and estradiol secretion in human granulosa cells. Hum Reprod (Oxford, England)., 27, 1790–1800 Reverchon, M., Bertoldo, M.J., Rame, C., Froment, P., Dupont, J. (2014). CHEMERIN (RARRES2) decreases in vitro granulosa cell steroidogenesis and blocks oocyte meiotic progression in bovine species. Biol Reprod., 90(5), 102. doi:10.1095/biolreprod.113.117044 Rocha, A.L., Oliveira, F.R., Azevedo, R.C. ve diğ. (2019). Recent advances in the understanding and management of polycystic ovary syndrome. F1000Res., 8, F1000 Faculty Rev-565. doi:10.12688/f1000research.15318.1 Schultz, S., Beck-Sickinger, A.G. (2013). Chemerin and vaspin: possible targets to treat obesity?. ChemMedChem., 8(4), 549–559. doi:10.1002/cmdc.201200448 Shapouri-Moghaddam, A., Mohammadian, S., Vazini, H., Taghadosi, M. , Esmaeili, S.A., Mardani, F. ve diğ. (2018). Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol., 233(9), 6425–6440. doi:10.1002/jcp.26429 Shi, J., Fan, J., Su, Q., Yang, Z. (2019). Cytokines and Abnormal Glucose and Lipid Metabolism. Front Endocrinol (Lausanne)., 10, 703. doi:10.3389/fendo.2019.00703 Skiba, M.A., Islam, R.M., Bell, R.J., Davis, S.R. (2018). Understanding variation in prevalence estimates of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update., 24(6), 694-709. doi: 10.1093/humupd/dmy022. Spritzer, P.M., Lecke, S.B., Satler, F., Morsch, D.M. (2015). Adipose Tissue Dysfunction, Adipokines, and Low-Grade Chronic Inflammation in Polycystic Ovary Syndrome. Reproduction., 149, R219–R227 Stein, I.F., Leventhal, M.L. (1935). Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol, 29, 181–91. Tan, B.K., Chen, J., Farhatullah, S., Adya, R., Kaur, J., Heutling, D. ve diğ. (2009). Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes., 58(9), 1971–1977. doi:10.2337/db08-1528 The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, (2004). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome: The Rotterdam ESHRE/ ASRM- Sponsered PCOS Consensus Workshop Group. Fertility & Sterility, 81(1), 19-25. Wang, F.F., Pan, J.X., Wu, Y., Zhu, Y.H., Hardiman, P.J., Qu, F. (2018). American, European, and Chinese practice guidelines or consensuses of polycystic ovary syndrome: a comparative analysis. J Zhejiang Univ Sci B., 19(5), 354-363. doi: 10.1631/jzus.B1700074. Wang, Q., Leader, A., Tsang, B.K. (2013). Inhibitory roles of prohibitin and chemerin in FSH-induced rat granulosa cell steroidogenesis. Endocrinology., 154(2), 956–967. doi:10.1210/en.2012-1836 Wang, Y. Huang, R., Li, X., Zhu, Q., Liao, Y.,Tao, T. ve diğ. (2019). High concentration of chemerin caused by ovarian hyperandrogenism may lead to poor IVF outcome in polycystic ovary syndrome: a pilot study. Gynecol Endocrinol., 35(12), 1072-1077. doi: 10.1080/09513590.2019.1622087. Wittamer, V., Franssen, J.D., Vulcano, M., Mirjolet, J.F., Le Poul, E., Migeotte, I. ve diğ. (2003). Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med., 198(7), 977–985. doi:10.1084/jem.20030382 Yildiz, B.O., Bozdag, G., Yapici, Z., Esinler, I., Yarali, H. (2012). Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod., 27, 3067–3073. Zawadzki, J.K., Dunaif, A. (1992). Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR, editors. Polycystic ovary syndrome. Boston: Blackwell Scientific Publications, 377–384. Zhao, L., Zhu, Z., Lou, H., Zhu, G., Huang, W., Zhang, S. ve diğ. (2016). Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): a meta-analysis. Oncotarget., 7(23), 33715–33721. doi:10.18632/oncotarget.9553 Zylla, S., Pietzner, M., Kühn, J.P., Völzke, H., Dörr, M., Nauck, M. ve diğ. (2017). Serum chemerin is associated with inflammatory and metabolic parameters-results of a population-based study. Obesity (Silver Spring)., 25(2), 468–475. doi:10.1002/oby.21735