AMPK Activation Is Important for the Preservation of Insulin Sensitivity in Visceral,but Not in Subcutaneous Adipose Tissue of Postnatally Overfed Rat Model of Polycystic Ovary Syndrome |
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Authors: | Bojana Mić ić ,Ana Teofilović ,Ana Djordjevic,Nataš a Velič ković ,Djuro Macut,Danijela Vojnović Milutinović |
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Affiliation: | 1.Department of Biochemistry, Institute for Biological Research “Siniša Stanković”, National Institute of 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 |
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Abstract: | Polycystic ovary syndrome (PCOS) is a well-known reproductive syndrome usually associated with obesity, insulin resistance, and hyperinsulinemia. Although the first signs of PCOS begin early in adolescence, it is underexplored whether peripubertal obesity predisposes women to PCOS metabolic disturbances. To highlight that, we examined the impact of postnatal overfeeding-induced obesity, achieved by litter size reduction during the suckling period, on metabolic disturbances associated with visceral and subcutaneous adipose tissue (VAT and SAT) function in the 5α-dihydrotestosterone (5α-DHT)-induced animal model of PCOS. We analyzed markers of insulin signaling, lipid metabolism, and energy sensing in the VAT and SAT. Our results showed that postnatally overfed DHT-treated Wistar rats had increased VAT mass with hypertrophic adipocytes, together with hyperinsulinemia and increased HOMA index. In the VAT of these animals, insulin signaling remained unchanged while lipogenic markers decreased, which was accompanied by increased AMPK activation. In the SAT of the same animals, markers of lipogenesis and lipolysis increased, while the activity of AMPK decreased. Taken together, obtained results showed that postnatal overfeeding predisposes development of PCOS systemic insulin resistance, most likely as a result of worsened metabolic function of SAT, while VAT preserved its tissue insulin sensitivity through increased activity of AMPK. |
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Keywords: | polycystic ovary syndrome, obesity, visceral adipose tissue, subcutaneous adipose tissue, insulin resistance, 5α -dihydrotestosterone, early postnatal overfeeding, lipogenesis, lipolysis, AMP-activated kinase |
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