DLK1 and Nesfatin-1 Levels and the Relationship with Metabolic Parameters in Polycystic Ovary Syndrome: Prospective, Controlled Study

Overview

Journal Turk J Obstet Gynecol

Specialty Gynecology & Obstetrics

Date 2021 Jun 4

PMID 34083652

Citations 9

Authors

Melike Demir Caltekin

Aysen Caniklioglu

Serenat Eris Yalcin

Demet Aydogan Kirmizi

Emre Baser

Ethem Serdar Yalvac

Affiliations

Soon will be listed here.

Abstract

Objective: Delta-like 1 (DLK1) is known to inhibit adipocyte differentiation and nesfatin-1 is a neuropeptide that plays a role in the regulation of nutrition and metabolism. We aimed to assess both the levels of DLK1 and nesfatin-1 in polycystic ovary syndrome (PCOS) and determine the association of DLK1 and nesfatin-1 with metabolic parameters.

Materials And Methods: Forty-four patients with PCOS and 40 healthy women as the control group were included in this study. Venous blood samples of the participants were collected, and hormonal, metabolic parameters, DLK1 and nesfatin-1 blood levels were determined. Anthropometric parameters were also determined. For a double comparison, the Mann-Whitney U test was used for non-parametric numerical data, and Student's t-test was used for parametric numerical data. Bivariate correlations were investigated using Spearman's correlation analysis. The diagnostic performance of the parameters was evaluated using receiver operating characteristic curve analysis.

Results: The findings showed that DLK1 and nesfatin-1 levels were lower among the PCOS group, and the differences in these values were found to be statistically significant. A significant negative correlation was found between DLK1 levels and body mass index (BMI), waist/hip ratio, visceral adiposity index (VAI), fasting serum insulin (FSI), homeostasis model of assessment-insulin resistance (HOMA-IR) and triglyceride levels. A significant negative correlation was found between nesfatin-1 levels and BMI, VAI, FSI, HOMA-IR and triglyceride.

Conclusion: The findings showed that DLK1 and nesfatin-1 levels were lower in PCOS. Based on this study, DLK1 may be culpable for metabolic disorders in PCOS and can be a novel marker for PCOS in the future.

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References

Mario F, Graff S, Spritzer P . Adiposity Indexes as Phenotype-Specific Markers of Preclinical Metabolic Alterations and Cardiovascular Risk in Polycystic Ovary Syndrome: A Cross-Sectional Study. Exp Clin Endocrinol Diabetes. 2017; 125(5):307-315. DOI: 10.1055/s-0042-119524. View

Lee K, Villena J, Moon Y, Kim K, Lee S, Kang C . Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1). J Clin Invest. 2003; 111(4):453-61. PMC: 151920. DOI: 10.1172/JCI15924. View

. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81(1):19-25. DOI: 10.1016/j.fertnstert.2003.10.004. View

Dauber A, Cunha-Silva M, Macedo D, Brito V, Abreu A, Roberts S . Paternally Inherited DLK1 Deletion Associated With Familial Central Precocious Puberty. J Clin Endocrinol Metab. 2017; 102(5):1557-1567. PMC: 5443333. DOI: 10.1210/jc.2016-3677. View

Kir Sahin F, Sahin S, Ural U, Cumhur Cure M, Senturk S, Bayoglu Tekin Y . Nesfatin-1 and Vitamin D levels may be associated with systolic and diastolic blood pressure values and hearth rate in polycystic ovary syndrome. Bosn J Basic Med Sci. 2015; 15(3):57-63. PMC: 4594327. DOI: 10.17305/bjbms.2015.432. View

Kopan R, Ilagan M . The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009; 137(2):216-33. PMC: 2827930. DOI: 10.1016/j.cell.2009.03.045. View

Nakata M, Manaka K, Yamamoto S, Mori M, Yada T . Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca(2+) influx through L-type channels in mouse islet β-cells. Endocr J. 2011; 58(4):305-13. DOI: 10.1507/endocrj.k11e-056. View

Kagami M, Nagasaki K, Kosaki R, Horikawa R, Naiki Y, Saitoh S . Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients. Genet Med. 2017; 19(12):1356-1366. PMC: 5729347. DOI: 10.1038/gim.2017.53. View

Ademoglu E, Gorar S, Carlioglu A, Yazici H, Dellal F, Berberoglu Z . Plasma nesfatin-1 levels are increased in patients with polycystic ovary syndrome. J Endocrinol Invest. 2014; 37(8):715-719. DOI: 10.1007/s40618-014-0089-2. View

10.

Kim J, Chung Y, Kim H, Im E, Lee H, Yang H . The Tissue Distribution of Nesfatin-1/NUCB2 in Mouse. Dev Reprod. 2015; 18(4):301-9. PMC: 4415639. DOI: 10.12717/devrep.2014.18.4.301. View

11.

Villena J, Choi C, Wang Y, Kim S, Hwang Y, Kim Y . Resistance to high-fat diet-induced obesity but exacerbated insulin resistance in mice overexpressing preadipocyte factor-1 (Pref-1): a new model of partial lipodystrophy. Diabetes. 2008; 57(12):3258-66. PMC: 2584131. DOI: 10.2337/db07-1739. View

12.

Moon Y, Smas C, Lee K, Villena J, Kim K, Yun E . Mice lacking paternally expressed Pref-1/Dlk1 display growth retardation and accelerated adiposity. Mol Cell Biol. 2002; 22(15):5585-92. PMC: 133956. DOI: 10.1128/MCB.22.15.5585-5592.2002. View

13.

Xu Y, Zhang H, Li Q, Lao K, Wang Y . The role of nesfatin-1 expression in letrozole-induced polycystic ovaries in the rat. Gynecol Endocrinol. 2017; 33(6):438-441. DOI: 10.1080/09513590.2017.1290068. View

14.

Rhee M, Lee S, Kim J, Ham D, Park H, Yang H . Preadipocyte factor 1 induces pancreatic ductal cell differentiation into insulin-producing cells. Sci Rep. 2016; 6:23960. PMC: 4820710. DOI: 10.1038/srep23960. View

15.

Deniz R, Gurates B, Aydin S, Celik H, Sahin I, Baykus Y . Nesfatin-1 and other hormone alterations in polycystic ovary syndrome. Endocrine. 2012; 42(3):694-9. DOI: 10.1007/s12020-012-9638-7. View

16.

Kucukler F, Gorkem U, Simsek Y, Kocabas R, Gulen S, Guler S . Low level of Nesfatin-1 is associated with gestational diabetes mellitus. Gynecol Endocrinol. 2016; 32(9):759-761. DOI: 10.1080/09513590.2016.1180679. View

17.

Legro R, Castracane V, Kauffman R . Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv. 2004; 59(2):141-54. DOI: 10.1097/01.OGX.0000109523.25076.E2. View

18.

Lee Y, Yun M, Kim H, Jeon B, Park B, Lee B . Exogenous administration of DLK1 ameliorates hepatic steatosis and regulates gluconeogenesis via activation of AMPK. Int J Obes (Lond). 2015; 40(2):356-65. DOI: 10.1038/ijo.2015.173. View

19.

Gonzalez R, Perry R, Gao X, Gaidhu M, Tsushima R, Ceddia R . Nutrient responsive nesfatin-1 regulates energy balance and induces glucose-stimulated insulin secretion in rats. Endocrinology. 2011; 152(10):3628-37. DOI: 10.1210/en.2010-1471. View

20.

Fica S, Albu A, Constantin M, Dobri G . Insulin resistance and fertility in polycystic ovary syndrome. J Med Life. 2010; 1(4):415-22. PMC: 3018970. View