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The Potential of SGLT-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: The Current Status and Future Perspectives
 
 
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Article

AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding

by
Bojana Mićić
1,
Ana Djordjevic
1,
Nataša Veličković
1,
Sanja Kovačević
1,
Teodora Martić
1,
Djuro Macut
2 and
Danijela Vojnović Milutinović
1,*
1
Department of Biochemistry, Institute for Biological Research “Siniša Stanković”-National Institute of the Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd, 11060 Belgrade, Serbia
2
Clinic for Endocrinology, Diabetes and Metabolic Diseases University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Doktora Subotića 13, 11000 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Biomedicines 2023, 11(6), 1586; https://doi.org/10.3390/biomedicines11061586
Submission received: 28 April 2023 / Revised: 21 May 2023 / Accepted: 27 May 2023 / Published: 30 May 2023
(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS) 2.0)

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age, often associated with obesity and insulin resistance. Childhood obesity is an important predisposing factor for the development of PCOS later in life. Being particularly interested in the interplay between prepubertal obesity and hyperandrogenemia, we investigated the effects of early postnatal overfeeding, accomplished by reducing litter size during the period of suckling, on energy sensing and insulin signaling pathways in the gastrocnemius muscle of a rat model of PCOS-induced by 5α-dihydrotestosterone (DHT). The combination of overfeeding and DHT treatment caused hyperinsulinemia and decreased systemic insulin sensitivity. Early postnatal overfeeding induced defects at critical nodes of the insulin signaling pathway in skeletal muscle, which was associated with reduced glucose uptake in the presence of hyperandrogenemia. In this setting, under a combination of overfeeding and DHT treatment, skeletal muscle switched to mitochondrial β-oxidation of fatty acids, resulting in oxidative stress and inflammation that stimulated AMP-activated protein kinase (AMPK) activity and its downstream targets involved in mitochondrial biogenesis and antioxidant protection. Overall, a combination of overfeeding and hyperandrogenemia resulted in a prooxidative and insulin-resistant state in skeletal muscle. This was accompanied by the activation of AMPK, which could represent a potential therapeutic target in insulin-resistant PCOS patients.
Keywords: PCOS; postnatal overfeeding; 5α-dihydrotestosterone; obesity; insulin resistance; skeletal muscle; AMPK; lipid metabolism; oxidative stress; mitochondrial β-oxidation PCOS; postnatal overfeeding; 5α-dihydrotestosterone; obesity; insulin resistance; skeletal muscle; AMPK; lipid metabolism; oxidative stress; mitochondrial β-oxidation

Share and Cite

MDPI and ACS Style

Mićić, B.; Djordjevic, A.; Veličković, N.; Kovačević, S.; Martić, T.; Macut, D.; Vojnović Milutinović, D. AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding. Biomedicines 2023, 11, 1586. https://doi.org/10.3390/biomedicines11061586

AMA Style

Mićić B, Djordjevic A, Veličković N, Kovačević S, Martić T, Macut D, Vojnović Milutinović D. AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding. Biomedicines. 2023; 11(6):1586. https://doi.org/10.3390/biomedicines11061586

Chicago/Turabian Style

Mićić, Bojana, Ana Djordjevic, Nataša Veličković, Sanja Kovačević, Teodora Martić, Djuro Macut, and Danijela Vojnović Milutinović. 2023. "AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding" Biomedicines 11, no. 6: 1586. https://doi.org/10.3390/biomedicines11061586

APA Style

Mićić, B., Djordjevic, A., Veličković, N., Kovačević, S., Martić, T., Macut, D., & Vojnović Milutinović, D. (2023). AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding. Biomedicines, 11(6), 1586. https://doi.org/10.3390/biomedicines11061586

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