GDF-15 and mtDNA Deletions Are Useful Biomarkers of Mitochondrial Dysfunction in Insulin Resistance and PCOS

Varhegyi, Vera; Modos, Anna; Trager, Domonkos; Gerszi, Dora; Horvath, Eszter Maria; Sipos, Miklos; Acs, Nandor; Molnar, Maria Judit; Varbiro, Szabolcs; Gal, Aniko

doi:10.3390/ijms252010916

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GDF-15 and mtDNA Deletions Are Useful Biomarkers of Mitochondrial Dysfunction in Insulin Resistance and PCOS

by

Vera Varhegyi

^1,2,

Anna Modos

^1,2,

Domonkos Trager

¹,

Dora Gerszi

²,

Eszter Maria Horvath

³,

Miklos Sipos

²,

Nandor Acs

²,

Maria Judit Molnar

¹,

Szabolcs Varbiro

^2,4,5,† and

Aniko Gal

^1,*,†

¹

Institute of Genomic Medicine and Rare Disorders, Semmelweis University, 1085 Budapest, Hungary

²

Department of Obstetrics and Gynecology, Semmelweis University, 1085 Budapest, Hungary

³

Department of Physiology, Semmelweis University, 1085 Budapest, Hungary

⁴

Department of Obstetrics and Gynecology, Albert Szent-Györgyi Clinical Centre, University of Szeged, 6720 Szeged, Hungary

⁵

Workgroup for Science Management, Doctoral School, Semmelweis University, 1085 Budapest, Hungary

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2024, 25(20), 10916; https://doi.org/10.3390/ijms252010916

Submission received: 2 September 2024 / Revised: 4 October 2024 / Accepted: 8 October 2024 / Published: 10 October 2024

(This article belongs to the Special Issue New Challenges and Perspectives in Polycystic Ovary Syndrome)

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Abstract

There is no literature available about the growth differentiation factor-15 (GDF-15) biomarker in combination with mitochondrial DNA (mtDNA) deletions in insulin resistance (IR), and polycystic ovary syndrome (PCOS); however, it would be useful to achieve optimal metabolic status and improve pregnancy success. In this study, the role of GDF-15 and mtDNA deletions as biomarkers in the pathogenesis of IR and PCOS was investigated. In our study, 81 female patients who were treated for IR and/or PCOS and 41 healthy controls were included. GDF-15 levels in patients showed a marked increase compared to controls. Elevated GDF-15 levels were found in 12 patients; all of them had a BMI > 25 kg/m², which is associated with reactive hyperinsulinemia. The presence of mitochondrial dysfunction was mainly observed in the IR-only subgroup. The increase in plasma levels of GDF-15 and the prevalence of mtDNA deletions is directly proportional to body mass index. The more marked metabolic abnormalities required more intensive drug therapy with a parallel increase in plasma GDF-15 levels. Elevated levels of GDF-15 and the presence of mitochondrial DNA deletions may be a consequence of carbohydrate metabolism disorders in patients and thus a predictor of the process of accelerated aging.

Keywords: PCOS; insulin resistance; GDF-15; mitochondrial dysfunction; mtDNA deletion

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MDPI and ACS Style

Varhegyi, V.; Modos, A.; Trager, D.; Gerszi, D.; Horvath, E.M.; Sipos, M.; Acs, N.; Molnar, M.J.; Varbiro, S.; Gal, A. GDF-15 and mtDNA Deletions Are Useful Biomarkers of Mitochondrial Dysfunction in Insulin Resistance and PCOS. Int. J. Mol. Sci. 2024, 25, 10916. https://doi.org/10.3390/ijms252010916

AMA Style

Varhegyi V, Modos A, Trager D, Gerszi D, Horvath EM, Sipos M, Acs N, Molnar MJ, Varbiro S, Gal A. GDF-15 and mtDNA Deletions Are Useful Biomarkers of Mitochondrial Dysfunction in Insulin Resistance and PCOS. International Journal of Molecular Sciences. 2024; 25(20):10916. https://doi.org/10.3390/ijms252010916

Chicago/Turabian Style

Varhegyi, Vera, Anna Modos, Domonkos Trager, Dora Gerszi, Eszter Maria Horvath, Miklos Sipos, Nandor Acs, Maria Judit Molnar, Szabolcs Varbiro, and Aniko Gal. 2024. "GDF-15 and mtDNA Deletions Are Useful Biomarkers of Mitochondrial Dysfunction in Insulin Resistance and PCOS" International Journal of Molecular Sciences 25, no. 20: 10916. https://doi.org/10.3390/ijms252010916

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GDF-15 and mtDNA Deletions Are Useful Biomarkers of Mitochondrial Dysfunction in Insulin Resistance and PCOS

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