@conference{
author = "Vojnović-Milutinović, Danijela and Veličković, Nataša and Radovanović, Marina and Đorđević, Ana and Brkljačić, Jelena and Teofilović, Ana and Bursać, Biljana and Jelača, Sanja and Macut, Đuro",
year = "2020",
abstract = "Polycystic ovary syndrome (PCOS) is a complex reproductive disorder that
is usually associated with metabolic disturbances such as obesity, dyslipidemia
and insulin resistance. In this study, female rats treated with nonaromatizable
5α dihydrotestosterone (DHT) were used as an animal model of
PCOS. The aim of this study was to assess the presence of inflammation in liver and visceral adipose tissue (VAT), which accompanies metabolic
disturbances in animal model of PCOS. Female (21 days old) Wistar rats
were treated subcutaneously with DHT pellets, while control animals received
placebo pellets. Glucose, triglycerides, free fatty acids (FFA) were
determined in blood plasma, while corticosterone was analyzed both in plasma
and liver. Expression of genes and proteinsinvolved in lipid metabolism,
such as sterol regulatory element binding protein1 (SREBP-1), fatty acid
synthase (FAS) and acetyl-CoA carboxylase (ACC), lipin-1, adipose tissue
triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), were analyzed
in the VAT of treated rats. Tissue inflammationevaluated by nuclear
factor kappa B (NFκB)protein level and intracellular distribution, as well as
by TNFα, IL6 and IL1β mRNA levels. Glucocorticoid signaling was examined
at the level of 11 beta hydroxysteroid dehydrogenase type 1 (11βHSD1)
and 5α-reductase, as well asby glucocorticoid receptor (GR) leveland its
subcellular distribution. The results showed that DHT treatment induced increase
of lipogenic factors (SREBP-1, lipin-1, FAS and PEPCK), while the
level of lipolytic enzyme HSL was decreasedin VAT. These molecular alterations
were accompanied by adipocyte hypertrophy, visceral obesity and
elevated plasma FFA and triglyceride concentrations. Those changes in lipid
metabolism were possible trigger for low-grade inflammation observed in
the VAT and characterized by NFκB activation and increasedIL6 and IL1β
mRNA levels. In spite of increased VAT proinflammatory mediators, the
level of proinflammatory cytokines, IL6 and IL1β, was decreased in the liver
of DHT-treated rats, while the activation of NFκB remained unchanged.
The state of suppressed inflammation in the liver could be an outcome of
stimulated glucocorticoid signaling, as judged byincreased hepatic corticosterone
level and GR activation. The augmentation of hepatic glucocorticoids
could be a net result of increased expression of 11βHSD1 and decreased
expression of 5β-reductase mRNA. In conclusion, the results showed that
abdominal obesity and dyslipidemia in the animal model of PCOS were accompanied
with hypertrophic adipocytes, lipid accumulation and low-grade
inflammation in the VAT. However, these metabolic disturbances did not resultin
hepatic inflammation due to increased tissue levels of glucocorticoids.",
publisher = "European Society of Endocrinology",
journal = "22nd European Congress of Endocrinology: Abstracts; 2020 Sep 5-9",
title = "Different effects of 5α-dihydrotestosterone treatment on hepatic and visceral adipose tissue inflammation in animal model of polycystic ovary syndrome",
doi = "10.1530/endoabs.70.AEP382",
pages = "AEP382"
}