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Cardiac fatty acid uptake and metabolism in the rat model of polycystic ovary syndrome

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Abstract

Polycystic ovary syndrome (PCOS) is associated with an altered plasma lipid profile and increased risk for cardiovascular diseases. We hypothesized that molecular mechanisms underlying cardiac pathology in PCOS involve changes in expression and subcellular localization of several key proteins involved in cardiac lipid transport and metabolism, such as fatty acid transporter CD36, lipin 1, peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ coactivator-1 (PGC1), and carnitine palmitoyltransferase 1 (CPT1). We used the animal model of PCOS obtained by treating female rats with dihydrotestosterone (DHT). Protein levels of CD36, lipin 1, PPARα, PGC1, and antioxidative enzymes were assessed by Western blot in different cardiac cell compartments. Cardiac triglycerides (TG) and lipid peroxidation were also measured. The content of CD36 was decreased in both the cardiac plasma membranes and intracellular pool. On the other hand, total content of cardiac lipin 1 in DHT-treated rats was elevated, in contrast to decreased microsomal lipin 1 content. An increase in nuclear content of lipin 1 was observed together with elevation of nuclear PPARα and PGC1, and an increase in CPT1 expression. However, lipid peroxidation was reduced in the heart, without alterations in antioxidative enzymes expression and cardiac TG content. The results indicate that treatment of female rats with DHT is accompanied by a decrease of fatty acid uptake and a reduction of lipid peroxidation in the heart. The observed elevation of lipin 1, PPARα, PGC1, and CPT1 expression suggests that cardiac fatty acid metabolism is shifted toward mitochondrial beta oxidation.

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Acknowledgments

This study was supported by the Project Grant No. III41009, from the Ministry of Education, Science and Technological Development, Republic of Serbia. Authors are particularly thankful to Marija Takić, from the Laboratory for Nutrition and Metabolism of the Institute for Medical Research, University of Belgrade, Serbia, for her assistance in the measurement of cardiac triglycerides.

Conflict of interest

The authors declare that they have no conflict of interest.

Compliance with Ethical Standards

All animal procedures were in compliance with the EU Directive (2010/63/EU) on the protection of animals used for experimental and other scientific purposes, and were approved by the Ethical Committee for the Use of Laboratory Animals of the Institute for Biological Research “Siniša Stanković”, University of Belgrade (No. 2-20/10).

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  1. Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, PO Box 522, 11001, Belgrade, Republic of Serbia

    Snežana Tepavčević, Mojca Stojiljković, Tijana Ćulafić & Goran Korićanac

  2. Department of Biochemistry, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Republic of Serbia

    Danijela Vojnović Milutinović, Marina Nikolić & Gordana Matić

  3. Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Republic of Serbia

    Djuro Macut & Ivana Božić-Antić

  4. CHC Bežanijska Kosa, Belgrade, Republic of Serbia

    Jelica Bjekić-Macut

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  1. Snežana Tepavčević
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Tepavčević, S., Milutinović, D.V., Macut, D. et al. Cardiac fatty acid uptake and metabolism in the rat model of polycystic ovary syndrome. Endocrine 50, 193–201 (2015). https://doi.org/10.1007/s12020-015-0558-1

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  • DOI: https://doi.org/10.1007/s12020-015-0558-1

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