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A possible connection between tumor necrosis factor alpha and adropin levels in polycystic ovary syndrome

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Abstract

Context

Adropin is a peptide hormone implicated in the regulation of insulin sensitivity and energy homeostasis. Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disease associated with insulin resistance. It has been demonstrated that various inflammatory markers increased in PCOS including TNF-α. TNF-α regulates the secretion of certain peptides which play a crucial role in glucose and lipid homeostasis. There is also some evidence of a link between TNF-α and adropin.

Objective

To ascertain whether there is an association between circulating adropin levels and TNF-α in PCOS.

Patients and design

152 women with PCOS and 152 age- and body mass index-matched controls without PCOS were recruited for this cross-sectional study.

Main outcome measures

Adropin and TNF-α levels were measured using ELISA.

Results

Adropin levels were lower in the PCOS group compared with the control group (7.43 ± 0.79 vs. 9.42 ± 0.76 ng/ml, P < 0.001), whereas TNF-α levels were higher (49.93 ± 3.39 vs. 35.83 ± 2.47 pg/ml, P < 0.001). A strongly negative correlation was found between circulating adropin levels and TNF-α levels in women with PCOS (r = −0.407, P < 0.001). Binary logistic regression analysis revealed that decreased adropin levels were significantly associated with high odds of having PCOS, although, after adjustment for TNF-α, this link vanished. Additionally, multiple linear regression analysis showed that HOMA-IR and TFN-α independently predicted adropin levels.

Conclusions

Serum adropin levels are significantly decreased in PCOS and are inversely associated with TNF-α. Further dissection of the nature of this association can open new therapeutic options for metabolic diseases.

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Abbreviations

AdrKO:

Adropin knockout mice

BMI:

Body mass index

CI:

Confidence interval

CV:

Coefficient of variability

E2 :

Estradiol

FBG:

Fasting blood glucose

FG:

Ferriman-Gallwey

HDL-C:

High density lipoprotein cholesterol

HOMA-IR:

Homeostasis model assessment of insulin resistance

hs-CRP:

High sensitivity C-reactive protein

HUVECs:

Human umbilical vein endothelial cells

LDL-C:

Low density lipoprotein cholesterol

OR:

Odds ratio

PCOS:

Polycystic ovary syndrome

TNF-α:

Tumor necrosis factor alpha

VIF:

Variance inflation factor

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Author contributions

T.K., M.C., G.U.K., and O.G.C. participated in study design and performed ELISA. T.K., M.C., P.Y. and M.B. participated in study design, analyzed the data, wrote, reviewed and edited the manuscript. O.Y, M.T. provided serum samples and contributed to discussions of data interpretation. M.C. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Department of Biochemistry and Clinical Biochemistry, Dokuz Eylul University Faculty of Medicine, 35340, Inciralti, Izmir, Turkey

    T. Kume & O. G. Calan

  2. Division of Endocrinology and Metabolism (PCOS Research Group), Department of Internal Medicine, Dokuz Eylul University Faculty of Medicine, 35340, Inciralti, Izmir, Turkey

    M. Calan

  3. Department of Obstetrics and Gynecology, Manisa Merkezefendi State Hospital, 45020, Merkezefendi, Manisa, Turkey

    O. Yilmaz & M. Temur

  4. Division of Endocrinology and Metabolism, Department of Internal Medicine (PCOS Research Group), Izmir Bozyaka Training and Research Hospital, 35170, Bozyaka, Izmir, Turkey

    G. U. Kocabas

  5. Department of Bioengineering, Ege University, 35100, Bornova, Izmir, Turkey

    P. Yesil

  6. Department of Obstetrics and Gynecology, Medical Park Hospital, Izmir University Faculty of Medicine, 35575, Izmir, Turkey

    M. Bicer

Authors
  1. T. Kume
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Corresponding author

Correspondence to M. Calan.

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The authors declare that they have no conflict of interest.

Ethical approval

The study was conducted in compliance with the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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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 39, 747–754 (2016). https://doi.org/10.1007/s40618-016-0453-5

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  • DOI: https://doi.org/10.1007/s40618-016-0453-5

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