TY  - CONF
AU  - Mićić, Bojana
AU  - Veličković, Nataša
AU  - Đorđević, Ana
AU  - Teofilović, Ana
AU  - Kovačević, Sanja
AU  - Radovanović, Marina
AU  - Brkljačić, Jelena
AU  - Macut Djuro
AU  - Vojnović Milutinović, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6418
AB  - 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.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding
SP  - 144
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6418
ER  - 

@conference{
author = "Mićić, Bojana and Veličković, Nataša and Đorđević, Ana and Teofilović, Ana and Kovačević, Sanja and Radovanović, Marina and Brkljačić, Jelena and Macut Djuro and Vojnović Milutinović, Danijela",
year = "2023",
abstract = "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.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding",
pages = "144",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6418"
}

Mićić, B., Veličković, N., Đorđević, A., Teofilović, A., Kovačević, S., Radovanović, M., Brkljačić, J., Macut Djuro,& Vojnović Milutinović, D.. (2023). Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding. in 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., 144.
https://hdl.handle.net/21.15107/rcub_ibiss_6418

Mićić B, Veličković N, Đorđević A, Teofilović A, Kovačević S, Radovanović M, Brkljačić J, Macut Djuro, Vojnović Milutinović D. Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:144.
https://hdl.handle.net/21.15107/rcub_ibiss_6418 .

Mićić, Bojana, Veličković, Nataša, Đorđević, Ana, Teofilović, Ana, Kovačević, Sanja, Radovanović, Marina, Brkljačić, Jelena, Macut Djuro, Vojnović Milutinović, Danijela, "Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):144,
https://hdl.handle.net/21.15107/rcub_ibiss_6418 .

TY  - JOUR
AU  - Macut, Đuro
AU  - Opalić, Milica
AU  - Popović, Bojana
AU  - Ognjanović, Sanja
AU  - Bjekić-Macut, Jelica
AU  - Livadas, Sarantis
AU  - Petrović, Tijana
AU  - Hrnčić, Dragan
AU  - Stanojlović, Olivera
AU  - Vojnović Milutinović, Danijela
AU  - Micić, Dragan
AU  - Mastorakos, George
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6329
AB  - Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at  different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period.
PB  - Bucharest: Acta Endocrinologica Foundation
T2  - Acta Endocrinologica (Bucharest)
T1  - The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update
IS  - 1
VL  - 19
DO  - 10.4183/aeb.2023.81
SP  - 81
EP  - 86
ER  - 

@article{
author = "Macut, Đuro and Opalić, Milica and Popović, Bojana and Ognjanović, Sanja and Bjekić-Macut, Jelica and Livadas, Sarantis and Petrović, Tijana and Hrnčić, Dragan and Stanojlović, Olivera and Vojnović Milutinović, Danijela and Micić, Dragan and Mastorakos, George",
year = "2023",
abstract = "Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at  different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period.",
publisher = "Bucharest: Acta Endocrinologica Foundation",
journal = "Acta Endocrinologica (Bucharest)",
title = "The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update",
number = "1",
volume = "19",
doi = "10.4183/aeb.2023.81",
pages = "81-86"
}

Macut, Đ., Opalić, M., Popović, B., Ognjanović, S., Bjekić-Macut, J., Livadas, S., Petrović, T., Hrnčić, D., Stanojlović, O., Vojnović Milutinović, D., Micić, D.,& Mastorakos, G.. (2023). The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update. in Acta Endocrinologica (Bucharest)
Bucharest: Acta Endocrinologica Foundation., 19(1), 81-86.
https://doi.org/10.4183/aeb.2023.81

Macut Đ, Opalić M, Popović B, Ognjanović S, Bjekić-Macut J, Livadas S, Petrović T, Hrnčić D, Stanojlović O, Vojnović Milutinović D, Micić D, Mastorakos G. The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update. in Acta Endocrinologica (Bucharest). 2023;19(1):81-86.
doi:10.4183/aeb.2023.81 .

Macut, Đuro, Opalić, Milica, Popović, Bojana, Ognjanović, Sanja, Bjekić-Macut, Jelica, Livadas, Sarantis, Petrović, Tijana, Hrnčić, Dragan, Stanojlović, Olivera, Vojnović Milutinović, Danijela, Micić, Dragan, Mastorakos, George, "The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update" in Acta Endocrinologica (Bucharest), 19, no. 1 (2023):81-86,
https://doi.org/10.4183/aeb.2023.81 . .

TY  - JOUR
AU  - Vojnović Milutinović, Danijela
AU  - Radovanović, Marina
AU  - Veličković, Nataša
AU  - Đorđević, Ana
AU  - Bursać, Biljana
AU  - Brkljačić, Jelena
AU  - Teofilović, Ana
AU  - Božić Antić, Ivana
AU  - Bjekić-Macut, Jelica
AU  - Shirif Zidane, Abdulbaset
AU  - Matić, Gordana
AU  - Macut, Đuro
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6331
AB  - Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome. 
Female Wistar rats were treated with nonaromatizable 5α dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.
Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α dihydrotestosterone-treated animals only at the systemic, and not at the level of visceral adipose tissue. 
The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity.
PB  - Stuttgart: Georg Thieme Verlag KG
T2  - Experimental and Clinical Endocrinology and Diabetes
T1  - Enhanced inflammation without impairment of insulin signaling in the visceral adipose tissue of 5α- dihydrotestosterone-induced animal model of polycystic ovary syndrome
IS  - 8
VL  - 125
DO  - 10.1055/s-0043-104531
SP  - 522
EP  - 529
ER  - 

@article{
author = "Vojnović Milutinović, Danijela and Radovanović, Marina and Veličković, Nataša and Đorđević, Ana and Bursać, Biljana and Brkljačić, Jelena and Teofilović, Ana and Božić Antić, Ivana and Bjekić-Macut, Jelica and Shirif Zidane, Abdulbaset and Matić, Gordana and Macut, Đuro",
year = "2017",
abstract = "Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome. 
Female Wistar rats were treated with nonaromatizable 5α dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.
Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α dihydrotestosterone-treated animals only at the systemic, and not at the level of visceral adipose tissue. 
The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity.",
publisher = "Stuttgart: Georg Thieme Verlag KG",
journal = "Experimental and Clinical Endocrinology and Diabetes",
title = "Enhanced inflammation without impairment of insulin signaling in the visceral adipose tissue of 5α- dihydrotestosterone-induced animal model of polycystic ovary syndrome",
number = "8",
volume = "125",
doi = "10.1055/s-0043-104531",
pages = "522-529"
}

Vojnović Milutinović, D., Radovanović, M., Veličković, N., Đorđević, A., Bursać, B., Brkljačić, J., Teofilović, A., Božić Antić, I., Bjekić-Macut, J., Shirif Zidane, A., Matić, G.,& Macut, Đ.. (2017). Enhanced inflammation without impairment of insulin signaling in the visceral adipose tissue of 5α- dihydrotestosterone-induced animal model of polycystic ovary syndrome. in Experimental and Clinical Endocrinology and Diabetes
Stuttgart: Georg Thieme Verlag KG., 125(8), 522-529.
https://doi.org/10.1055/s-0043-104531

Vojnović Milutinović D, Radovanović M, Veličković N, Đorđević A, Bursać B, Brkljačić J, Teofilović A, Božić Antić I, Bjekić-Macut J, Shirif Zidane A, Matić G, Macut Đ. Enhanced inflammation without impairment of insulin signaling in the visceral adipose tissue of 5α- dihydrotestosterone-induced animal model of polycystic ovary syndrome. in Experimental and Clinical Endocrinology and Diabetes. 2017;125(8):522-529.
doi:10.1055/s-0043-104531 .

Vojnović Milutinović, Danijela, Radovanović, Marina, Veličković, Nataša, Đorđević, Ana, Bursać, Biljana, Brkljačić, Jelena, Teofilović, Ana, Božić Antić, Ivana, Bjekić-Macut, Jelica, Shirif Zidane, Abdulbaset, Matić, Gordana, Macut, Đuro, "Enhanced inflammation without impairment of insulin signaling in the visceral adipose tissue of 5α- dihydrotestosterone-induced animal model of polycystic ovary syndrome" in Experimental and Clinical Endocrinology and Diabetes, 125, no. 8 (2017):522-529,
https://doi.org/10.1055/s-0043-104531 . .

TY  - JOUR
AU  - Macut, Djuro
AU  - Božić Antić, Ivana
AU  - Bjekić-Macut, Jelica
AU  - Panidis, Dimitrios
AU  - Tziomalos, Konstantinos
AU  - Vojnović Milutinović, Danijela
AU  - Stanojlović, Olivera
AU  - Kastratović-Kotlica, Biljana
AU  - Petakov, Milan
AU  - Milić, Nataša
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6332
AB  - OBJECTIVE: There is a need for a simple and accurate method for the assessment of cardiovascular risk in polycystic ovary syndrome (PCOS). Lipid accumulation product (LAP) is based on the assessment of waist circumference and serum triglycerides that yield an estimation of lipid overaccumulation. We aimed to determine whether LAP is associated with metabolic syndrome (MetS) in Caucasian women with PCOS. DESIGN: We studied 222 women with PCOS who were diagnosed using the Rotterdam criteria. In all the subjects and controls, LAP was determined and the MetS was assessed using three different international criteria, NCEP-ATP III, IDF, and JIS. ROC curve and logistic regression analyses were performed to determine and analyze associations with the MetS. RESULTS: In the study population the prevalence of MetS was 16.2–19.4%. The cut-off value of 25.9 determined that LAP has the strongest association with MetS whichever international criteria are used, followed by HDL (NCEP-ATP III and JIS) and glucose (IDF). CONCLUSIONS: LAP is used as an independent clinical indicator for MetS in our PCOS women of Caucasian origin. The high diagnostic accuracy of LAP is superseding the need for the use of multiple clinical indicators for the assessment of lipid accumulation as a prerequisite for diagnosis of metabolic and cardiovascular diseases in PCOS women.
PB  - Springer Nature
T2  - Hormones
T1  - Lipid accumulation product is associated with metabolic syndrome in women with polycystic ovary syndrome
VL  - 15
DO  - 10.1007/BF03401401
SP  - 35
EP  - 44
ER  - 

@article{
author = "Macut, Djuro and Božić Antić, Ivana and Bjekić-Macut, Jelica and Panidis, Dimitrios and Tziomalos, Konstantinos and Vojnović Milutinović, Danijela and Stanojlović, Olivera and Kastratović-Kotlica, Biljana and Petakov, Milan and Milić, Nataša",
year = "2016",
abstract = "OBJECTIVE: There is a need for a simple and accurate method for the assessment of cardiovascular risk in polycystic ovary syndrome (PCOS). Lipid accumulation product (LAP) is based on the assessment of waist circumference and serum triglycerides that yield an estimation of lipid overaccumulation. We aimed to determine whether LAP is associated with metabolic syndrome (MetS) in Caucasian women with PCOS. DESIGN: We studied 222 women with PCOS who were diagnosed using the Rotterdam criteria. In all the subjects and controls, LAP was determined and the MetS was assessed using three different international criteria, NCEP-ATP III, IDF, and JIS. ROC curve and logistic regression analyses were performed to determine and analyze associations with the MetS. RESULTS: In the study population the prevalence of MetS was 16.2–19.4%. The cut-off value of 25.9 determined that LAP has the strongest association with MetS whichever international criteria are used, followed by HDL (NCEP-ATP III and JIS) and glucose (IDF). CONCLUSIONS: LAP is used as an independent clinical indicator for MetS in our PCOS women of Caucasian origin. The high diagnostic accuracy of LAP is superseding the need for the use of multiple clinical indicators for the assessment of lipid accumulation as a prerequisite for diagnosis of metabolic and cardiovascular diseases in PCOS women.",
publisher = "Springer Nature",
journal = "Hormones",
title = "Lipid accumulation product is associated with metabolic syndrome in women with polycystic ovary syndrome",
volume = "15",
doi = "10.1007/BF03401401",
pages = "35-44"
}

Macut, D., Božić Antić, I., Bjekić-Macut, J., Panidis, D., Tziomalos, K., Vojnović Milutinović, D., Stanojlović, O., Kastratović-Kotlica, B., Petakov, M.,& Milić, N.. (2016). Lipid accumulation product is associated with metabolic syndrome in women with polycystic ovary syndrome. in Hormones
Springer Nature., 15, 35-44.
https://doi.org/10.1007/BF03401401

Macut D, Božić Antić I, Bjekić-Macut J, Panidis D, Tziomalos K, Vojnović Milutinović D, Stanojlović O, Kastratović-Kotlica B, Petakov M, Milić N. Lipid accumulation product is associated with metabolic syndrome in women with polycystic ovary syndrome. in Hormones. 2016;15:35-44.
doi:10.1007/BF03401401 .

Macut, Djuro, Božić Antić, Ivana, Bjekić-Macut, Jelica, Panidis, Dimitrios, Tziomalos, Konstantinos, Vojnović Milutinović, Danijela, Stanojlović, Olivera, Kastratović-Kotlica, Biljana, Petakov, Milan, Milić, Nataša, "Lipid accumulation product is associated with metabolic syndrome in women with polycystic ovary syndrome" in Hormones, 15 (2016):35-44,
https://doi.org/10.1007/BF03401401 . .