Contribution of early postnatal overfeeding to metabolic disorders in animal model of polycystic ovary syndrome
Doprinos povećanog kalorijskog unosa u ranom postnatalnom periodu razvoju metaboličkih poremećaja u animalnom modelu sindroma policističnih jajnika
Abstract:
Polycystic ovary syndrome (PCOS) is a reproductive disorder based on hyperandrogenemia but also associated with metabolic complications. PCOS can occur in girls before puberty, and the increase in body weight at this age predisposes them to later development of the syndrome.
Increased caloric intake in the perinatal period, easily mimicked in rodents by manipulating litter size, affects neuroendocrine programming and leads to hyperphagia and weight gain, as well as earlier onset of puberty. The aim of this doctoral dissertation was to examine the contribution of increased caloric intake in early postnatal period to the development of metabolic disorders associated with the syndrome using an animal model of PCOS. An animal model of PCOS induced by 5α-dihydrotestosterone was additionally challenged with caloric excess by litter size reduction to induce prepubertal obesity. Parameters of systemic insulin sensitivity and lipid status were analyzed, as were markers of insulin signaling and energy metabolism at the level of visceral (VAT) and subcutaneous (SAT) adipose tissue and skeletal muscle. The combination of treatments resulted in systemic hyperinsulinemia and decreased insulin sensitivity. Despite adipocyte hypertrophy, insulin sensitivity is maintained at the VAT level, likely due to activation of AMPK. The absence of SAT proliferation and the concomitantly activated lipolytic and lipogenic metabolic pathways suggest its dysfunction. Skeletal muscles in conditions of reduced sensitivity to insulin use fatty acids as an energy substrate, and activation of AMPK contributes to the functionality of this tissue by increasing the rate of β-oxidation. Our results suggest that weight gain before puberty predisposes to the development of insulin resistance in PCOS, while interaction with hyperandrogenemia is critical for its full manifestation.
Keywords:
PCOS; prepubertal weight gain; 5α-dihydrotestosterone; hyperandrogenemia; early postnatal overfeeding; visceral adipose tissue; subcutaneous adipose tissue; skeletal muscle; insulin resistance; hyperinsulinemiaSource:
University of Belgrade, Faculty of Biology, 2023, 1-88Funding / 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)