Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding
2023
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Authors:
Mićić, BojanaVeličković, Nataša
Đorđević, Ana
Teofilović, Ana
Kovačević, Sanja
Radovanović, Marina
Brkljačić, Jelena
Macut Djuro
Vojnović Milutinović, Danijela
Contributors
Dubljević, ZoranaDocument Type:
Conference object (Published version)
,
© 2023 by the Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
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Show full item recordAbstract:
Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women’s
fertility and metabolic health throughout their life time. Insulin resistance and obesity, in conjunction
with excess androgens, are undeniably involved in its development. We aimed to elucidate how hyperandrogenemia
and prepubertal adiposity contribute to the development of metabolic disturbances in
rat model of PCOS.
Methods: The animal model of PCOS induced by 5a-dihydrotestosterone (DHT) was additionally challenged
by litter size reduction (LSR) during suckling period, to ensure overfeeding and development of
prepubertal adiposity. Systemic parameters of insulin sensitivity, along with markers of energy sensing,
insulin signaling, and lipid metabolism were analyzed in visceral adipose tissue (VAT) and skeletal muscle.
Results: The combination of treatments led to hyperinsulinemia and impaired systemic insulin sensitivity.
This was not accompanied with altered insulin signaling in the VAT, in spite of observed adipocytes
hypertrophy probably due to activation of AMPK and restrained lipogenesis in this tissue. On the other
hand, insulin signaling in skeletal muscle was impaired, which resulted in increased muscle fatty acid
uptake and oxidation after combined treatment. The switch to fatty acids oxidation subsequently led to
oxidative stress and inflammation, which was followed by adaptive activation of AMPK and increased
expression of its targets involved in antioxidant protection and mitochondrial biogenesis.
Conclusion: Our results suggest that prepubertal weight gain predisposes to insulin resistance development
in androgen-excess PCOS. The protective activation of AMPK in VAT and muscle makes it a potential
therapeutic target for insulin-resistant PCOS patients.
Keywords:
polycystic ovary syndrome; early postnatal overfeeding; insulin resistance; adipose tissue; skeletal muscleFunding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Dobrijević Z, editor. Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade ; 2023. p. 144. (Trends in Molecular Biology; Special Issue).