TY  - JOUR
AU  - Paunović, Marija
AU  - Milošević, Maja
AU  - Mitrović-Ajtić, Olivera
AU  - Veličković, Nataša
AU  - Mićić, Bojana
AU  - Nedić, Olgica
AU  - Todorović, Vanja
AU  - Vučić, Vesna
AU  - Petrović, Snježana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6684
AB  - Diets high in fat and sugar lead to metabolic syndrome (MetS) and related chronic diseases. We
investigated the effects of commercially available, cold-pressed polyphenol-rich black currant
(BC) and cornelian cherry (CC) juices on the prevention of MetS in Wistar rats induced by a 10-
weeks high-fat high-fructose (HFF) diet. Juice consumption, either BC or CC, with a HFF diet
resulted in lower serum triglycerides compared to only the HFF consumption. Both juices also
mitigated the effects of HFF on the liver, pancreas, and adipose tissue, by preserving liver and
pancreas histomorphology and reducing visceral fat and adipocyte size. Furthermore, supple-
mentation with both juices reduced glucagon and up-regulated insulin expression in the pancreas
of the rats on the HFF diet, whereas the BC also showed improved glucose regulation. BC juice
also reduced the expression of IL-6 and hepatic inflammation compared to the group only on HFF
diet. Both juices, especially BC, could be a convenient solution for the prevention of MetS in
humans.
PB  - Elsevier Ltd.
T2  - Heliyon
T1  - Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats
IS  - 7
VL  - 10
DO  - 10.1016/j.heliyon.2024.e27709
SP  - e27709
ER  - 

@article{
author = "Paunović, Marija and Milošević, Maja and Mitrović-Ajtić, Olivera and Veličković, Nataša and Mićić, Bojana and Nedić, Olgica and Todorović, Vanja and Vučić, Vesna and Petrović, Snježana",
year = "2024",
abstract = "Diets high in fat and sugar lead to metabolic syndrome (MetS) and related chronic diseases. We
investigated the effects of commercially available, cold-pressed polyphenol-rich black currant
(BC) and cornelian cherry (CC) juices on the prevention of MetS in Wistar rats induced by a 10-
weeks high-fat high-fructose (HFF) diet. Juice consumption, either BC or CC, with a HFF diet
resulted in lower serum triglycerides compared to only the HFF consumption. Both juices also
mitigated the effects of HFF on the liver, pancreas, and adipose tissue, by preserving liver and
pancreas histomorphology and reducing visceral fat and adipocyte size. Furthermore, supple-
mentation with both juices reduced glucagon and up-regulated insulin expression in the pancreas
of the rats on the HFF diet, whereas the BC also showed improved glucose regulation. BC juice
also reduced the expression of IL-6 and hepatic inflammation compared to the group only on HFF
diet. Both juices, especially BC, could be a convenient solution for the prevention of MetS in
humans.",
publisher = "Elsevier Ltd.",
journal = "Heliyon",
title = "Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats",
number = "7",
volume = "10",
doi = "10.1016/j.heliyon.2024.e27709",
pages = "e27709"
}

Paunović, M., Milošević, M., Mitrović-Ajtić, O., Veličković, N., Mićić, B., Nedić, O., Todorović, V., Vučić, V.,& Petrović, S.. (2024). Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats. in Heliyon
Elsevier Ltd.., 10(7), e27709.
https://doi.org/10.1016/j.heliyon.2024.e27709

Paunović M, Milošević M, Mitrović-Ajtić O, Veličković N, Mićić B, Nedić O, Todorović V, Vučić V, Petrović S. Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats. in Heliyon. 2024;10(7):e27709.
doi:10.1016/j.heliyon.2024.e27709 .

Paunović, Marija, Milošević, Maja, Mitrović-Ajtić, Olivera, Veličković, Nataša, Mićić, Bojana, Nedić, Olgica, Todorović, Vanja, Vučić, Vesna, Petrović, Snježana, "Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats" in Heliyon, 10, no. 7 (2024):e27709,
https://doi.org/10.1016/j.heliyon.2024.e27709 . .

TY  - CONF
AU  - Petrović, Snježana
AU  - Paunović, Marija
AU  - Veličković, Nataša
AU  - Mićić, Bojana
AU  - Milošević, Maja
AU  - Arsić, Aleksandra
AU  - Pokimica, Biljana
AU  - Vučić, Vesna
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6683
AB  - Our study was aimed to investigate the effects of commercially available, cold-pressed polyphenol-rich black currant (BC) juice on fat accumulation, blood lipids, insulin resistance, high blood pressure, and inflammation, in rats placed on high-fat high-fructose (HFF) diet. Coadministration of BC juice significantly reduced diet-induced adiposity and plasma triglycerides levels, improved glucose tolerance, and suppressed hepatic inflammation during prolonged HFF feeding in rats. These findings suggest that consumption of BC juice may  counter the harmful effects of the Western diet rich in fats and sugars, and to be useful for the prevention of metabolic syndrome development and progression.
PB  - Čačak: Faculty of Agronomy in Čačak, University of Kragujevac
C3  - Proceedings: 2nd International Symposium on Biotechnology: SYMBIOTECH; 2024 Mar 14–15; Čačak, Serbia
T1  - Polyphenol-rich black currant juice ameliorates metabolic syndrome induced by high-fat diet in rats
SP  - 595
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6683
ER  - 

@conference{
author = "Petrović, Snježana and Paunović, Marija and Veličković, Nataša and Mićić, Bojana and Milošević, Maja and Arsić, Aleksandra and Pokimica, Biljana and Vučić, Vesna",
year = "2024",
abstract = "Our study was aimed to investigate the effects of commercially available, cold-pressed polyphenol-rich black currant (BC) juice on fat accumulation, blood lipids, insulin resistance, high blood pressure, and inflammation, in rats placed on high-fat high-fructose (HFF) diet. Coadministration of BC juice significantly reduced diet-induced adiposity and plasma triglycerides levels, improved glucose tolerance, and suppressed hepatic inflammation during prolonged HFF feeding in rats. These findings suggest that consumption of BC juice may  counter the harmful effects of the Western diet rich in fats and sugars, and to be useful for the prevention of metabolic syndrome development and progression.",
publisher = "Čačak: Faculty of Agronomy in Čačak, University of Kragujevac",
journal = "Proceedings: 2nd International Symposium on Biotechnology: SYMBIOTECH; 2024 Mar 14–15; Čačak, Serbia",
title = "Polyphenol-rich black currant juice ameliorates metabolic syndrome induced by high-fat diet in rats",
pages = "595",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6683"
}

Petrović, S., Paunović, M., Veličković, N., Mićić, B., Milošević, M., Arsić, A., Pokimica, B.,& Vučić, V.. (2024). Polyphenol-rich black currant juice ameliorates metabolic syndrome induced by high-fat diet in rats. in Proceedings: 2nd International Symposium on Biotechnology: SYMBIOTECH; 2024 Mar 14–15; Čačak, Serbia
Čačak: Faculty of Agronomy in Čačak, University of Kragujevac., 595.
https://hdl.handle.net/21.15107/rcub_ibiss_6683

Petrović S, Paunović M, Veličković N, Mićić B, Milošević M, Arsić A, Pokimica B, Vučić V. Polyphenol-rich black currant juice ameliorates metabolic syndrome induced by high-fat diet in rats. in Proceedings: 2nd International Symposium on Biotechnology: SYMBIOTECH; 2024 Mar 14–15; Čačak, Serbia. 2024;:595.
https://hdl.handle.net/21.15107/rcub_ibiss_6683 .

Petrović, Snježana, Paunović, Marija, Veličković, Nataša, Mićić, Bojana, Milošević, Maja, Arsić, Aleksandra, Pokimica, Biljana, Vučić, Vesna, "Polyphenol-rich black currant juice ameliorates metabolic syndrome induced by high-fat diet in rats" in Proceedings: 2nd International Symposium on Biotechnology: SYMBIOTECH; 2024 Mar 14–15; Čačak, Serbia (2024):595,
https://hdl.handle.net/21.15107/rcub_ibiss_6683 .

TY  - THES
AU  - Mićić, Bojana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6457
AB  - Sindrom policističnih jajnika (PCOS) je reproduktivni poremećaj u čijoj osnovi je hiperandrogenemija, ali ga prate i metaboličke komplikacije. 
PCOS se može javiti u prepubertetskom uzrastu, a povećanje telesne mase tokom ovog uzrasta predisponira za kasniji razvoj sindroma. Kalorijski suficit u perinatalnom periodu, koji se kod glodara postiže manipulacijom veličine legla, utiče na neuroendokrino programiranje, dovodeći do gojenja i ranijeg nastupanja puberteta. Cilj ove disertacije je bio da se na animalnom modelu PCOS ispita doprinos povećanog kalorijskog unosa u ranom postnatalnom periodu razvoju metaboličkih poremećaja udruženih sa sindromom. Model PCOS je kreiran tretmanom ženki pacova 5α-dihidrotestosteronom (DHT), a prepubertetska gojaznost postignuta kalorijskim suficitom kroz smanjenje veličine legla. 
Analizirani su parametri sistemske insulinske osetljivosti i lipidni status, kao i markeri insulinske signalizacije i energetskog metabolizma na nivou visceralnog (VAT) i subkutanog (SAT) masnog tkiva i skeletnih mišića. DHT tretman u kombinaciji sa povećanim kalorijskim unosom je uslovio sistemsku hiperinsulinemiju i smanjenje insulinske osetljivosti. 
Uprkos hipertrofiji adipocita, insulinska osetljivost na nivou VAT je očuvana, verovatno usled aktivacije AMPK. Izostanak proliferacije SAT i istovremeno aktivirani lipolitički i lipogeni putevi ukazuju na njegovu disfunkcionalnost. Skeletni mišići u uslovima smanjene osetljivosti na insulin koriste masne kiseline kao energetski supstrat, a aktivacija AMPK doprinosi funkcionalnosti tkiva kroz povećanje stope β-oksidacije. 
Dobijeni rezultati sugerišu da povećanje telesne mase pre puberteta predisponira razvoj insulinske rezistencije u PCOS, dok je za njeno puno ispoljavanje ključna interakcija sa hiperandrogenemijom.
AB  - 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.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Contribution of early postnatal overfeeding to metabolic disorders in animal model of polycystic ovary syndrome
T1  - Doprinos povećanog kalorijskog unosa u ranom postnatalnom periodu razvoju metaboličkih poremećaja u animalnom modelu sindroma policističnih jajnika
SP  - 1
EP  - 88
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6457
ER  - 

@phdthesis{
author = "Mićić, Bojana",
year = "2023",
abstract = "Sindrom policističnih jajnika (PCOS) je reproduktivni poremećaj u čijoj osnovi je hiperandrogenemija, ali ga prate i metaboličke komplikacije. 
PCOS se može javiti u prepubertetskom uzrastu, a povećanje telesne mase tokom ovog uzrasta predisponira za kasniji razvoj sindroma. Kalorijski suficit u perinatalnom periodu, koji se kod glodara postiže manipulacijom veličine legla, utiče na neuroendokrino programiranje, dovodeći do gojenja i ranijeg nastupanja puberteta. Cilj ove disertacije je bio da se na animalnom modelu PCOS ispita doprinos povećanog kalorijskog unosa u ranom postnatalnom periodu razvoju metaboličkih poremećaja udruženih sa sindromom. Model PCOS je kreiran tretmanom ženki pacova 5α-dihidrotestosteronom (DHT), a prepubertetska gojaznost postignuta kalorijskim suficitom kroz smanjenje veličine legla. 
Analizirani su parametri sistemske insulinske osetljivosti i lipidni status, kao i markeri insulinske signalizacije i energetskog metabolizma na nivou visceralnog (VAT) i subkutanog (SAT) masnog tkiva i skeletnih mišića. DHT tretman u kombinaciji sa povećanim kalorijskim unosom je uslovio sistemsku hiperinsulinemiju i smanjenje insulinske osetljivosti. 
Uprkos hipertrofiji adipocita, insulinska osetljivost na nivou VAT je očuvana, verovatno usled aktivacije AMPK. Izostanak proliferacije SAT i istovremeno aktivirani lipolitički i lipogeni putevi ukazuju na njegovu disfunkcionalnost. Skeletni mišići u uslovima smanjene osetljivosti na insulin koriste masne kiseline kao energetski supstrat, a aktivacija AMPK doprinosi funkcionalnosti tkiva kroz povećanje stope β-oksidacije. 
Dobijeni rezultati sugerišu da povećanje telesne mase pre puberteta predisponira razvoj insulinske rezistencije u PCOS, dok je za njeno puno ispoljavanje ključna interakcija sa hiperandrogenemijom., 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.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "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",
pages = "1-88",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6457"
}

Mićić, B.. (2023). Contribution of early postnatal overfeeding to metabolic disorders in animal model of polycystic ovary syndrome. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-88.
https://hdl.handle.net/21.15107/rcub_ibiss_6457

Mićić B. Contribution of early postnatal overfeeding to metabolic disorders in animal model of polycystic ovary syndrome. in University of Belgrade, Faculty of Biology. 2023;:1-88.
https://hdl.handle.net/21.15107/rcub_ibiss_6457 .

Mićić, Bojana, "Contribution of early postnatal overfeeding to metabolic disorders in animal model of polycystic ovary syndrome" in University of Belgrade, Faculty of Biology (2023):1-88,
https://hdl.handle.net/21.15107/rcub_ibiss_6457 .

TY  - CONF
AU  - Vratarić, Miloš
AU  - Teofilović, Ana
AU  - Vojnović Milutinović, Danijela
AU  - Veličković, Nataša
AU  - Bursać, Biljana
AU  - Gligorovska, Ljupka
AU  - Mićić, Bojana
AU  - Jovanović, Mirna
AU  - Đorđević, Ana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6419
AB  - Introduction: High-fat diet primarily leads to obesity but it can also lead to obesity resistant (OR) phenotype
with various metabolic complications. Liver plays central role in modulating lipid metabolism in
response to dyslipidemia induced by adipose tissue hypertrophy. The aim of this study was to define key
regulatory points that adjust lipid metabolism in the liver of OR mice on high-fat diet (HFD).
Methods:Male C57BL/6J mice were divided into two groups: control group on normal diet (10 kcal% fat,
D12450J, Research Diets, USA) and HFD group (60 kcal% fat, D12492, Research Diets, USA). After 14 weeks,
mice on HFD were classified as obese or OR based on 30% difference in body weight gain compared
with controls. Liver sections were analyzed histologically, while alterations in hepatic lipid metabolism
were assessed by qPCR and Western blot.
Results: Although HFD restricted hepatic de novo lipogenesis, increased influx of free fatty acids (FFA)
led to accumulation of lipid droplets in the liver of obese mice. In OR mice, liver morphology was restored,
as was expression of insulin sensitive sterol regulatory element-binding protein 1c (SREBP-1c).
Level of FFA transporter CD36 was reduced, whereas higher expression of diacylglycerol acyltransferase
2 limited lipotoxicity in OR compared with obese mice. FFA β-oxidation remained unchanged in both
HFD groups.
Conclusion: Lower FFA input and reduced lipid storage and lipotoxicity in the liver of OR mice suggest
that dyslipidemic complications associated with obesity could be ameliorated by targeted modulation
of expression of FFA transporters and regulators of lipid droplet formation.
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  - Modulation of hepatic lipid metabolism in obesity-resistant mice on a high-fat diet
SP  - 147
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6419
ER  - 

@conference{
author = "Vratarić, Miloš and Teofilović, Ana and Vojnović Milutinović, Danijela and Veličković, Nataša and Bursać, Biljana and Gligorovska, Ljupka and Mićić, Bojana and Jovanović, Mirna and Đorđević, Ana",
year = "2023",
abstract = "Introduction: High-fat diet primarily leads to obesity but it can also lead to obesity resistant (OR) phenotype
with various metabolic complications. Liver plays central role in modulating lipid metabolism in
response to dyslipidemia induced by adipose tissue hypertrophy. The aim of this study was to define key
regulatory points that adjust lipid metabolism in the liver of OR mice on high-fat diet (HFD).
Methods:Male C57BL/6J mice were divided into two groups: control group on normal diet (10 kcal% fat,
D12450J, Research Diets, USA) and HFD group (60 kcal% fat, D12492, Research Diets, USA). After 14 weeks,
mice on HFD were classified as obese or OR based on 30% difference in body weight gain compared
with controls. Liver sections were analyzed histologically, while alterations in hepatic lipid metabolism
were assessed by qPCR and Western blot.
Results: Although HFD restricted hepatic de novo lipogenesis, increased influx of free fatty acids (FFA)
led to accumulation of lipid droplets in the liver of obese mice. In OR mice, liver morphology was restored,
as was expression of insulin sensitive sterol regulatory element-binding protein 1c (SREBP-1c).
Level of FFA transporter CD36 was reduced, whereas higher expression of diacylglycerol acyltransferase
2 limited lipotoxicity in OR compared with obese mice. FFA β-oxidation remained unchanged in both
HFD groups.
Conclusion: Lower FFA input and reduced lipid storage and lipotoxicity in the liver of OR mice suggest
that dyslipidemic complications associated with obesity could be ameliorated by targeted modulation
of expression of FFA transporters and regulators of lipid droplet formation.",
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 = "Modulation of hepatic lipid metabolism in obesity-resistant mice on a high-fat diet",
pages = "147",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6419"
}

Vratarić, M., Teofilović, A., Vojnović Milutinović, D., Veličković, N., Bursać, B., Gligorovska, L., Mićić, B., Jovanović, M.,& Đorđević, A.. (2023). Modulation of hepatic lipid metabolism in obesity-resistant mice on a high-fat diet. 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., 147.
https://hdl.handle.net/21.15107/rcub_ibiss_6419

Vratarić M, Teofilović A, Vojnović Milutinović D, Veličković N, Bursać B, Gligorovska L, Mićić B, Jovanović M, Đorđević A. Modulation of hepatic lipid metabolism in obesity-resistant mice on a high-fat diet. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:147.
https://hdl.handle.net/21.15107/rcub_ibiss_6419 .

Vratarić, Miloš, Teofilović, Ana, Vojnović Milutinović, Danijela, Veličković, Nataša, Bursać, Biljana, Gligorovska, Ljupka, Mićić, Bojana, Jovanović, Mirna, Đorđević, Ana, "Modulation of hepatic lipid metabolism in obesity-resistant mice on a high-fat diet" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):147,
https://hdl.handle.net/21.15107/rcub_ibiss_6419 .

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  - Mićić, Bojana
AU  - Đorđević, Ana
AU  - Veličković, Nataša
AU  - Kovačević, Sanja
AU  - Martić, Teodora
AU  - Macut, Đuro
AU  - Vojnović-Milutinović, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5785
AB  - Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive
age, often associated with obesity and insulin resistance. Childhood obesity is an important
predisposing factor for the development of PCOS later in life. Being particularly interested in the
interplay between prepubertal obesity and hyperandrogenemia, we investigated the effects of early
postnatal overfeeding, accomplished by reducing litter size during the period of suckling, on energy
sensing and insulin signaling pathways in the gastrocnemius muscle of a rat model of PCOS-induced
by 5 -dihydrotestosterone (DHT). The combination of overfeeding and DHT treatment caused hyperinsulinemia
and decreased systemic insulin sensitivity. Early postnatal overfeeding induced defects
at critical nodes of the insulin signaling pathway in skeletal muscle, which was associated with
reduced glucose uptake in the presence of hyperandrogenemia. In this setting, under a combination
of overfeeding and DHT treatment, skeletal muscle switched to mitochondrial  -oxidation of fatty
acids, resulting in oxidative stress and inflammation that stimulated AMP-activated protein kinase
(AMPK) activity and its downstream targets involved in mitochondrial biogenesis and antioxidant
protection. Overall, a combination of overfeeding and hyperandrogenemia resulted in a prooxidative
and insulin-resistant state in skeletal muscle. This was accompanied by the activation of AMPK,
which could represent a potential therapeutic target in insulin-resistant PCOS patients.
PB  - Basel: MDPI
T2  - Biomedicines
T1  - AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding
IS  - 6
VL  - 11
DO  - 10.3390/biomedicines11061586
SP  - 1586
ER  - 

@article{
author = "Mićić, Bojana and Đorđević, Ana and Veličković, Nataša and Kovačević, Sanja and Martić, Teodora and Macut, Đuro and Vojnović-Milutinović, Danijela",
year = "2023",
abstract = "Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive
age, often associated with obesity and insulin resistance. Childhood obesity is an important
predisposing factor for the development of PCOS later in life. Being particularly interested in the
interplay between prepubertal obesity and hyperandrogenemia, we investigated the effects of early
postnatal overfeeding, accomplished by reducing litter size during the period of suckling, on energy
sensing and insulin signaling pathways in the gastrocnemius muscle of a rat model of PCOS-induced
by 5 -dihydrotestosterone (DHT). The combination of overfeeding and DHT treatment caused hyperinsulinemia
and decreased systemic insulin sensitivity. Early postnatal overfeeding induced defects
at critical nodes of the insulin signaling pathway in skeletal muscle, which was associated with
reduced glucose uptake in the presence of hyperandrogenemia. In this setting, under a combination
of overfeeding and DHT treatment, skeletal muscle switched to mitochondrial  -oxidation of fatty
acids, resulting in oxidative stress and inflammation that stimulated AMP-activated protein kinase
(AMPK) activity and its downstream targets involved in mitochondrial biogenesis and antioxidant
protection. Overall, a combination of overfeeding and hyperandrogenemia resulted in a prooxidative
and insulin-resistant state in skeletal muscle. This was accompanied by the activation of AMPK,
which could represent a potential therapeutic target in insulin-resistant PCOS patients.",
publisher = "Basel: MDPI",
journal = "Biomedicines",
title = "AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding",
number = "6",
volume = "11",
doi = "10.3390/biomedicines11061586",
pages = "1586"
}

Mićić, B., Đorđević, A., Veličković, N., Kovačević, S., Martić, T., Macut, Đ.,& Vojnović-Milutinović, D.. (2023). AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding. in Biomedicines
Basel: MDPI., 11(6), 1586.
https://doi.org/10.3390/biomedicines11061586

Mićić B, Đorđević A, Veličković N, Kovačević S, Martić T, Macut Đ, Vojnović-Milutinović D. AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding. in Biomedicines. 2023;11(6):1586.
doi:10.3390/biomedicines11061586 .

Mićić, Bojana, Đorđević, Ana, Veličković, Nataša, Kovačević, Sanja, Martić, Teodora, Macut, Đuro, Vojnović-Milutinović, Danijela, "AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding" in Biomedicines, 11, no. 6 (2023):1586,
https://doi.org/10.3390/biomedicines11061586 . .

TY  - JOUR
AU  - Ignjatović, Đurđica
AU  - Tovilović-Kovačević, Gordana
AU  - Mićić, Bojana
AU  - Tomić, Mirko
AU  - Đorđević, Ana
AU  - Macut, Đuro
AU  - Vojnović-Milutinović, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5821
AB  - Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine and metabolic abnormalities such as obesity and insulin resistance. PCOS is also associated with psychiatric disorders and cognitive impairment. The animal model of PCOS was induced by treating rats with 5α dihydrotestosterone (5α-DHT) and additionally modified to induce adiposity by litter size reduction (LSR). Spatial learning and memory were assessed using the Barnes Maze test, and striatal markers of synaptic plasticity were analyzed. Striatal insulin signaling was estimated by the levels of insulin receptor substrate 1 (IRS1), its inhibitory phosphorylation at Ser307, and glycogen synthase kinase-3α/β (GSK3α/β) activity. Both LSR and DHT treatment significantly decreased striatal protein levels of IRS1, followed by increased GSK3α/β activity in small litters. Results of the behavioral study showed that LSR had a negative effect on learning rate and memory retention, whereas DHT treatment did not induce impairment in memory formation. While protein levels of synaptophysin, GAP43, and postsynaptic density protein 95 (PSD-95) were not altered by the treatments, DHT treatment induced an increasein phosphorylation of PSD-95 at Ser295 in both normal and small litters. This study revealed that LSR and DHT treatment suppressed insulin signaling by downregulating IRS1 in the striatum. However, DHT treatment did not have an adverse effect on learning and memory, probably due to compensatory elevation in pPSD-95-Ser295, which had a positive effect on synaptic strength. This implies that hyperandrogenemia in this setting does not represent a threat to spatial learning and memory, opposite to the effect of overnutrition-related adiposity.
PB  - Amsterdam: Elsevier
T2  - Hormones and Behavior
T1  - Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome
VL  - 153
DO  - 10.1016/j.yhbeh.2023.105392
SP  - 105392
ER  - 

@article{
author = "Ignjatović, Đurđica and Tovilović-Kovačević, Gordana and Mićić, Bojana and Tomić, Mirko and Đorđević, Ana and Macut, Đuro and Vojnović-Milutinović, Danijela",
year = "2023",
abstract = "Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine and metabolic abnormalities such as obesity and insulin resistance. PCOS is also associated with psychiatric disorders and cognitive impairment. The animal model of PCOS was induced by treating rats with 5α dihydrotestosterone (5α-DHT) and additionally modified to induce adiposity by litter size reduction (LSR). Spatial learning and memory were assessed using the Barnes Maze test, and striatal markers of synaptic plasticity were analyzed. Striatal insulin signaling was estimated by the levels of insulin receptor substrate 1 (IRS1), its inhibitory phosphorylation at Ser307, and glycogen synthase kinase-3α/β (GSK3α/β) activity. Both LSR and DHT treatment significantly decreased striatal protein levels of IRS1, followed by increased GSK3α/β activity in small litters. Results of the behavioral study showed that LSR had a negative effect on learning rate and memory retention, whereas DHT treatment did not induce impairment in memory formation. While protein levels of synaptophysin, GAP43, and postsynaptic density protein 95 (PSD-95) were not altered by the treatments, DHT treatment induced an increasein phosphorylation of PSD-95 at Ser295 in both normal and small litters. This study revealed that LSR and DHT treatment suppressed insulin signaling by downregulating IRS1 in the striatum. However, DHT treatment did not have an adverse effect on learning and memory, probably due to compensatory elevation in pPSD-95-Ser295, which had a positive effect on synaptic strength. This implies that hyperandrogenemia in this setting does not represent a threat to spatial learning and memory, opposite to the effect of overnutrition-related adiposity.",
publisher = "Amsterdam: Elsevier",
journal = "Hormones and Behavior",
title = "Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome",
volume = "153",
doi = "10.1016/j.yhbeh.2023.105392",
pages = "105392"
}

Ignjatović, Đ., Tovilović-Kovačević, G., Mićić, B., Tomić, M., Đorđević, A., Macut, Đ.,& Vojnović-Milutinović, D.. (2023). Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome. in Hormones and Behavior
Amsterdam: Elsevier., 153, 105392.
https://doi.org/10.1016/j.yhbeh.2023.105392

Ignjatović Đ, Tovilović-Kovačević G, Mićić B, Tomić M, Đorđević A, Macut Đ, Vojnović-Milutinović D. Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome. in Hormones and Behavior. 2023;153:105392.
doi:10.1016/j.yhbeh.2023.105392 .

Ignjatović, Đurđica, Tovilović-Kovačević, Gordana, Mićić, Bojana, Tomić, Mirko, Đorđević, Ana, Macut, Đuro, Vojnović-Milutinović, Danijela, "Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome" in Hormones and Behavior, 153 (2023):105392,
https://doi.org/10.1016/j.yhbeh.2023.105392 . .

TY  - JOUR
AU  - Ignjatović, Đurđica
AU  - Tovilović-Kovačević, Gordana
AU  - Mićić, Bojana
AU  - Tomić, Mirko
AU  - Đorđević, Ana
AU  - Macut, Đuro
AU  - Vojnović-Milutinović, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5820
AB  - Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine and metabolic abnormalities such as obesity and insulin resistance. PCOS is also associated with psychiatric disorders and cognitive impairment. The animal model of PCOS was induced by treating rats with 5α dihydrotestosterone (5α-DHT) and additionally modified to induce adiposity by litter size reduction (LSR). Spatial learning and memory were assessed using the Barnes Maze test, and striatal markers of synaptic plasticity were analyzed. Striatal insulin signaling was estimated by the levels of insulin receptor substrate 1 (IRS1), its inhibitory phosphorylation at Ser307, and glycogen synthase kinase-3α/β (GSK3α/β) activity. Both LSR and DHT treatment significantly decreased striatal protein levels of IRS1, followed by increased GSK3α/β activity in small litters. Results of the behavioral study showed that LSR had a negative effect on learning rate and memory retention, whereas DHT treatment did not induce impairment in memory formation. While protein levels of synaptophysin, GAP43, and postsynaptic density protein 95 (PSD-95) were not altered by the treatments, DHT treatment induced an increase
in phosphorylation of PSD-95 at Ser295 in both normal and small litters. This study revealed that LSR and DHT treatment suppressed insulin signaling by downregulating IRS1 in the striatum. However, DHT treatment did not have an adverse effect on learning and memory, probably due to compensatory elevation in pPSD-95-Ser295, which had a positive effect on synaptic strength. This implies that hyperandrogenemia in this setting does not represent a threat to spatial learning and memory, opposite to the effect of overnutrition-related adiposity.
PB  - Amsterdam: Elsevier
T2  - Hormones and Behavior
T1  - Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome
VL  - 153
DO  - 10.1016/j.yhbeh.2023.105392
SP  - 105392
ER  - 

@article{
author = "Ignjatović, Đurđica and Tovilović-Kovačević, Gordana and Mićić, Bojana and Tomić, Mirko and Đorđević, Ana and Macut, Đuro and Vojnović-Milutinović, Danijela",
year = "2023",
abstract = "Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine and metabolic abnormalities such as obesity and insulin resistance. PCOS is also associated with psychiatric disorders and cognitive impairment. The animal model of PCOS was induced by treating rats with 5α dihydrotestosterone (5α-DHT) and additionally modified to induce adiposity by litter size reduction (LSR). Spatial learning and memory were assessed using the Barnes Maze test, and striatal markers of synaptic plasticity were analyzed. Striatal insulin signaling was estimated by the levels of insulin receptor substrate 1 (IRS1), its inhibitory phosphorylation at Ser307, and glycogen synthase kinase-3α/β (GSK3α/β) activity. Both LSR and DHT treatment significantly decreased striatal protein levels of IRS1, followed by increased GSK3α/β activity in small litters. Results of the behavioral study showed that LSR had a negative effect on learning rate and memory retention, whereas DHT treatment did not induce impairment in memory formation. While protein levels of synaptophysin, GAP43, and postsynaptic density protein 95 (PSD-95) were not altered by the treatments, DHT treatment induced an increase
in phosphorylation of PSD-95 at Ser295 in both normal and small litters. This study revealed that LSR and DHT treatment suppressed insulin signaling by downregulating IRS1 in the striatum. However, DHT treatment did not have an adverse effect on learning and memory, probably due to compensatory elevation in pPSD-95-Ser295, which had a positive effect on synaptic strength. This implies that hyperandrogenemia in this setting does not represent a threat to spatial learning and memory, opposite to the effect of overnutrition-related adiposity.",
publisher = "Amsterdam: Elsevier",
journal = "Hormones and Behavior",
title = "Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome",
volume = "153",
doi = "10.1016/j.yhbeh.2023.105392",
pages = "105392"
}

Ignjatović, Đ., Tovilović-Kovačević, G., Mićić, B., Tomić, M., Đorđević, A., Macut, Đ.,& Vojnović-Milutinović, D.. (2023). Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome. in Hormones and Behavior
Amsterdam: Elsevier., 153, 105392.
https://doi.org/10.1016/j.yhbeh.2023.105392

Ignjatović Đ, Tovilović-Kovačević G, Mićić B, Tomić M, Đorđević A, Macut Đ, Vojnović-Milutinović D. Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome. in Hormones and Behavior. 2023;153:105392.
doi:10.1016/j.yhbeh.2023.105392 .

Ignjatović, Đurđica, Tovilović-Kovačević, Gordana, Mićić, Bojana, Tomić, Mirko, Đorđević, Ana, Macut, Đuro, Vojnović-Milutinović, Danijela, "Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome" in Hormones and Behavior, 153 (2023):105392,
https://doi.org/10.1016/j.yhbeh.2023.105392 . .

TY  - JOUR
AU  - Mićić, Bojana
AU  - Teofilović, Ana
AU  - Đorđević, Ana
AU  - Veličković, Nataša
AU  - Macut, Djuro
AU  - Vojnović-Milutinović, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5022
AB  - 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 overfeedinginduced
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
5 -dihydrotestosterone (5 -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.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - 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
IS  - 16
VL  - 23
DO  - 10.3390/ijms23168942
SP  - 8942
ER  - 

@article{
author = "Mićić, Bojana and Teofilović, Ana and Đorđević, Ana and Veličković, Nataša and Macut, Djuro and Vojnović-Milutinović, Danijela",
year = "2022",
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 overfeedinginduced
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
5 -dihydrotestosterone (5 -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.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "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",
number = "16",
volume = "23",
doi = "10.3390/ijms23168942",
pages = "8942"
}

Mićić, B., Teofilović, A., Đorđević, A., Veličković, N., Macut, D.,& Vojnović-Milutinović, D.. (2022). 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. in International Journal of Molecular Sciences
Basel: MDPI., 23(16), 8942.
https://doi.org/10.3390/ijms23168942

Mićić B, Teofilović A, Đorđević A, Veličković N, Macut D, Vojnović-Milutinović D. 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. in International Journal of Molecular Sciences. 2022;23(16):8942.
doi:10.3390/ijms23168942 .

Mićić, Bojana, Teofilović, Ana, Đorđević, Ana, Veličković, Nataša, Macut, Djuro, Vojnović-Milutinović, Danijela, "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" in International Journal of Molecular Sciences, 23, no. 16 (2022):8942,
https://doi.org/10.3390/ijms23168942 . .

TY  - CONF
AU  - Mićić, Bojana
AU  - Radovanović, Marina
AU  - Tovilović-Kovačević, Gordana
AU  - Teofilović, Ana
AU  - Gligorovska, Ljupka
AU  - Vojnović-Milutinović, Danijela
AU  - Đorđević, Ana
AU  - Ignjatović, Đurđica
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4718
AB  - Fructose intake is associated with low-grade inflammation and increased oxidative
stress. Among long chain polyunsaturated fatty acids (LC-PUFAs), Ω-6 are recognized as a
contributing factor to inflammation, while Ω-3 LC-PUFAs are considered as functional foods with
beneficial effects, including inhibition of pro-inflammatory pathways. The aim of this study was to
analyze combined effects of physiologically relevant LC-PUFAs and fructose on inflammation and
antioxidant enzymes in the in vitro model of vascular endothelial cells. We examined the effects
of 0.5 mM fructose, alone and in combination with Ω-6 (arachidonic (AA) and linoleic (LA)) and
Ω-3 (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) LC-PUFAs on expression of pro-
inflammatory cytokines (tumor necrosis factor α (TNFα) and interleukin 6 (IL6)) in EA.hy926 cells.
The protein levels of nuclear factor-κB (NF-κB) and IB, as well as its phosphorylation, together
with superoxide dismutase (SOD) 1 and 2, catalase and glutathione reductase (GR) were also
analyzed. Total ROS amounts were determined using flow cytometric analysis of cells stained
with redox sensitive dihydrorhodamine 123 dye. The results showed that treatment of cells with
fructose increased TNFα and decreased IL6 mRNA levels. Additional treatment with LA, DHA
and EPA reduced TNFα and led to further decrease of IL6 expression. The observed changes
were not associated with NFB activation. All examined enzymes were unchanged after fructose
treatment, while GR was increased by LC-PUFA addition. SOD2 was reduced in cells treated
with AA, LA and EPA, while increased ROS amounts were observed with AA, DHA and EPA. This
was also evident in combined treatment with fructose. These preliminary results suggest that
LC-PUFAs, besides effect on pro-inflammatory cytokines, reduce SOD2 levels and increase ROS.
The increased levels of ROS could stimulate production of PUFA-derived peroxides, which in
GSH-enriched environment might be converted into anti-inflammatory derivatives, additionally
suppressing inflammation in fructose treated endothelial cells
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells
DO  - 10.1016/j.freeradbiomed.2021.08.092
SP  - S79
ER  - 

@conference{
author = "Mićić, Bojana and Radovanović, Marina and Tovilović-Kovačević, Gordana and Teofilović, Ana and Gligorovska, Ljupka and Vojnović-Milutinović, Danijela and Đorđević, Ana and Ignjatović, Đurđica",
year = "2021",
abstract = "Fructose intake is associated with low-grade inflammation and increased oxidative
stress. Among long chain polyunsaturated fatty acids (LC-PUFAs), Ω-6 are recognized as a
contributing factor to inflammation, while Ω-3 LC-PUFAs are considered as functional foods with
beneficial effects, including inhibition of pro-inflammatory pathways. The aim of this study was to
analyze combined effects of physiologically relevant LC-PUFAs and fructose on inflammation and
antioxidant enzymes in the in vitro model of vascular endothelial cells. We examined the effects
of 0.5 mM fructose, alone and in combination with Ω-6 (arachidonic (AA) and linoleic (LA)) and
Ω-3 (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) LC-PUFAs on expression of pro-
inflammatory cytokines (tumor necrosis factor α (TNFα) and interleukin 6 (IL6)) in EA.hy926 cells.
The protein levels of nuclear factor-κB (NF-κB) and IB, as well as its phosphorylation, together
with superoxide dismutase (SOD) 1 and 2, catalase and glutathione reductase (GR) were also
analyzed. Total ROS amounts were determined using flow cytometric analysis of cells stained
with redox sensitive dihydrorhodamine 123 dye. The results showed that treatment of cells with
fructose increased TNFα and decreased IL6 mRNA levels. Additional treatment with LA, DHA
and EPA reduced TNFα and led to further decrease of IL6 expression. The observed changes
were not associated with NFB activation. All examined enzymes were unchanged after fructose
treatment, while GR was increased by LC-PUFA addition. SOD2 was reduced in cells treated
with AA, LA and EPA, while increased ROS amounts were observed with AA, DHA and EPA. This
was also evident in combined treatment with fructose. These preliminary results suggest that
LC-PUFAs, besides effect on pro-inflammatory cytokines, reduce SOD2 levels and increase ROS.
The increased levels of ROS could stimulate production of PUFA-derived peroxides, which in
GSH-enriched environment might be converted into anti-inflammatory derivatives, additionally
suppressing inflammation in fructose treated endothelial cells",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells",
doi = "10.1016/j.freeradbiomed.2021.08.092",
pages = "S79"
}

Mićić, B., Radovanović, M., Tovilović-Kovačević, G., Teofilović, A., Gligorovska, L., Vojnović-Milutinović, D., Đorđević, A.,& Ignjatović, Đ.. (2021). Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., S79.
https://doi.org/10.1016/j.freeradbiomed.2021.08.092

Mićić B, Radovanović M, Tovilović-Kovačević G, Teofilović A, Gligorovska L, Vojnović-Milutinović D, Đorđević A, Ignjatović Đ. Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:S79.
doi:10.1016/j.freeradbiomed.2021.08.092 .

Mićić, Bojana, Radovanović, Marina, Tovilović-Kovačević, Gordana, Teofilović, Ana, Gligorovska, Ljupka, Vojnović-Milutinović, Danijela, Đorđević, Ana, Ignjatović, Đurđica, "Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):S79,
https://doi.org/10.1016/j.freeradbiomed.2021.08.092 . .