Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance

ObjectiveOxidative stress and mitochondrial dysfunction are implicated in polycystic ovary syndrome (PCOS). The present study assesses the effect of metformin treatment on mitochondrial function in polymorphonuclear cells from PCOS subjects. Additionally, we evaluate endocrine parameters and levels...

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Published in:European journal of endocrinology 2015-11, Vol.173 (5), p.683-691
Main Authors: Victor, Victor M, Rovira-Llopis, Susana, Bañuls, Celia, Diaz-Morales, Noelia, Castelló, Raquel, Falcón, Rosa, Gómez, Marcelino, Rocha, Milagros, Hernández-Mijares, Antonio
Format: Article
Language:English
Subjects:
Adult
Clinical study
Female
Humans
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - pharmacology
Insulin Resistance
Interleukin-6 - metabolism
Metformin - administration & dosage
Metformin - pharmacology
Mitochondria - drug effects
Mitochondria - metabolism
Neutrophils - drug effects
Neutrophils - metabolism
Polycystic Ovary Syndrome - drug therapy
Polycystic Ovary Syndrome - metabolism
Treatment Outcome
Tumor Necrosis Factor-alpha - drug effects
Young Adult
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Summary:ObjectiveOxidative stress and mitochondrial dysfunction are implicated in polycystic ovary syndrome (PCOS). The present study assesses the effect of metformin treatment on mitochondrial function in polymorphonuclear cells from PCOS subjects. Additionally, we evaluate endocrine parameters and levels of interleukin 6 (IL6) and tumour necrosis factor alpha (TNFα).Design and methodsOur study population was comprised of 35 women of reproductive age diagnosed with PCOS and treated with metformin for 12 weeks, and their corresponding controls (n=41), adjusted by age and BMI. We evaluated the alteration of endocrinological and anthropometrical parameters and androgen levels. Mitochondrial O2 consumption (using a Clark-type O2 electrode), membrane potential, mitochondrial mass, and levels of reactive oxygen species (ROS) and glutathione (GSH) (by means of fluorescence microscopy) were assessed in poymorphonuclear cells. H2O2 was evaluated with the Amplex RedR H2O2/Peroxidase Assay kit. IL6 and TNFα were measured using the Luminex 200 flow analyser system.ResultsMetformin had beneficial effects on patients by increasing mitochondrial O2 consumption, membrane potential, mitochondrial mass and glutathione levels, and by decreasing levels of reactive oxygen species and H2O2. In addition, metformin reduced glucose, follicle-stimulating hormone, IL6 and TNFα levels and increased dehydroepiandrosterone sulfate levels. HOMA-IR and mitochondrial function biomarkers positively correlated with ROS production (r=0.486, P=0.025), GSH content (r=0.710, P=0.049) and H2O2 (r=0.837, P=0.010), and negatively correlated with membrane potential (r=−0.829, P=0.011) at baseline. These differences disappeared after metformin treatment.ConclusionsOur results demonstrate the beneficial effects of metformin treatment on mitochondrial function in leukocytes of PCOS patients.
ISSN:0804-4643
1479-683X
DOI:10.1530/EJE-15-0572