Macut, Djuro

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  • Macut, Djuro (6)
  • Macut, Đuro (5)
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Author's Bibliography

Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome

Ignjatović, Đurđica; Tovilović-Kovačević, Gordana; Mićić, Bojana; Tomić, Mirko; Đorđević, Ana; Macut, Đuro; Vojnović-Milutinović, Danijela

(Amsterdam: Elsevier, 2023)

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 . .
6
1
1

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

Mićić, Bojana; Đorđević, Ana; Veličković, Nataša; Kovačević, Sanja; Martić, Teodora; Macut, Đuro; Vojnović-Milutinović, Danijela

(Basel: MDPI, 2023)

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 . .
2

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

Mićić, Bojana; Teofilović, Ana; Đorđević, Ana; Veličković, Nataša; Macut, Djuro; Vojnović-Milutinović, Danijela

(Basel: MDPI, 2022)

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 . .
3
3

A decade in female reproduction: an endocrine view of the past and into the future.

Macut, Đuro; Vojnović-Milutinović, Danijela; Rašić-Marković, Aleksandra; Brkljačić, Jelena; Bjekić-Macut, Jelica; Stanojlović, Olivera

(2018)

TY  - JOUR
AU  - Macut, Đuro
AU  - Vojnović-Milutinović, Danijela
AU  - Rašić-Marković, Aleksandra
AU  - Brkljačić, Jelena
AU  - Bjekić-Macut, Jelica
AU  - Stanojlović, Olivera
PY  - 2018
UR  - http://link.springer.com/10.1007/s42000-018-0073-x
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3220
AB  - Over the last decade, huge achievements have been made in the fields of neurophysiology, molecular endocrinology, and biochemistry, as well as in the successful translation of clinical research into diseases into clinical practice. As regards female reproduction, most of the advances made in this area were achieved in gonadal axis regulation, regulation of behavior through sex steroids, reproductive genetics, preservation of ovarian reproductive function, steroid profiling, and metabolic and overall reproductive outcomes. The coming years are expected to bring further understanding of the relationships between nutrition, energy metabolism, and reproductive function and to succeed in identifying new genetic markers linked to adverse metabolic and unfavorable cardiovascular outcomes in women. From our perspective, future research in the field of female reproduction should be directed toward doing research into genetic reproductive abnormalities and neuroendocrine diseases, pathophysiology, long-term health outcomes for oligo/amenorrhea, hyperandrogenism, and ovulatory dysfunction. It is additionally expected that a better understanding will be gained of the endocrinology of the placenta and of pregnancy, the role of the microbiome in female reproduction, the role of insulin sensitizers, anti-obesity and anti-diabetic drugs, and various advances in the prevention of ovarian damage caused by various oncology therapies, while new therapeutic options for the treatment of infertility, including kisspeptin, will be developed.
T2  - Hormones (Athens, Greece)
T1  - A decade in female reproduction: an endocrine view of the past and into the future.
IS  - 4
VL  - 17
DO  - 10.1007/s42000-018-0073-x
SP  - 497
EP  - 505
ER  - 
@article{
author = "Macut, Đuro and Vojnović-Milutinović, Danijela and Rašić-Marković, Aleksandra and Brkljačić, Jelena and Bjekić-Macut, Jelica and Stanojlović, Olivera",
year = "2018",
abstract = "Over the last decade, huge achievements have been made in the fields of neurophysiology, molecular endocrinology, and biochemistry, as well as in the successful translation of clinical research into diseases into clinical practice. As regards female reproduction, most of the advances made in this area were achieved in gonadal axis regulation, regulation of behavior through sex steroids, reproductive genetics, preservation of ovarian reproductive function, steroid profiling, and metabolic and overall reproductive outcomes. The coming years are expected to bring further understanding of the relationships between nutrition, energy metabolism, and reproductive function and to succeed in identifying new genetic markers linked to adverse metabolic and unfavorable cardiovascular outcomes in women. From our perspective, future research in the field of female reproduction should be directed toward doing research into genetic reproductive abnormalities and neuroendocrine diseases, pathophysiology, long-term health outcomes for oligo/amenorrhea, hyperandrogenism, and ovulatory dysfunction. It is additionally expected that a better understanding will be gained of the endocrinology of the placenta and of pregnancy, the role of the microbiome in female reproduction, the role of insulin sensitizers, anti-obesity and anti-diabetic drugs, and various advances in the prevention of ovarian damage caused by various oncology therapies, while new therapeutic options for the treatment of infertility, including kisspeptin, will be developed.",
journal = "Hormones (Athens, Greece)",
title = "A decade in female reproduction: an endocrine view of the past and into the future.",
number = "4",
volume = "17",
doi = "10.1007/s42000-018-0073-x",
pages = "497-505"
}
Macut, Đ., Vojnović-Milutinović, D., Rašić-Marković, A., Brkljačić, J., Bjekić-Macut, J.,& Stanojlović, O.. (2018). A decade in female reproduction: an endocrine view of the past and into the future.. in Hormones (Athens, Greece), 17(4), 497-505.
https://doi.org/10.1007/s42000-018-0073-x
Macut Đ, Vojnović-Milutinović D, Rašić-Marković A, Brkljačić J, Bjekić-Macut J, Stanojlović O. A decade in female reproduction: an endocrine view of the past and into the future.. in Hormones (Athens, Greece). 2018;17(4):497-505.
doi:10.1007/s42000-018-0073-x .
Macut, Đuro, Vojnović-Milutinović, Danijela, Rašić-Marković, Aleksandra, Brkljačić, Jelena, Bjekić-Macut, Jelica, Stanojlović, Olivera, "A decade in female reproduction: an endocrine view of the past and into the future." in Hormones (Athens, Greece), 17, no. 4 (2018):497-505,
https://doi.org/10.1007/s42000-018-0073-x . .
5
2
4

Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome

Božić-Antić, Ivana; Ilić, Dušan; Bjekić-Macut, Jelica; Bogavac, Tamara; Vojnović-Milutinović, Danijela; Kastratovic-Kotlica, Biljana; Milić, Nataša; Stanojlović, Olivera; Andrić, Zoran; Macut, Djuro

(2016)

TY  - JOUR
AU  - Božić-Antić, Ivana
AU  - Ilić, Dušan
AU  - Bjekić-Macut, Jelica
AU  - Bogavac, Tamara
AU  - Vojnović-Milutinović, Danijela
AU  - Kastratovic-Kotlica, Biljana
AU  - Milić, Nataša
AU  - Stanojlović, Olivera
AU  - Andrić, Zoran
AU  - Macut, Djuro
PY  - 2016
UR  - http://www.eje-online.org/lookup/doi/10.1530/EJE-16-0775
UR  - https://www.scopus.com/record/display.uri?eid=2-s2.0-85000384361&origin=SingleRecordEmailAlert&dgcid=scalert_sc_search_email&txGid=691E27A4B52E4CB98111082A19AFDEEC.wsnAw8kcdt7IPYLO0V48gA%3A9#
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2482
AB  - Objective: There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. Design: Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. Methods: In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. Results: All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. Conclusion: LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B.
T2  - European Journal of Endocrinology
T1  - Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome
IS  - 6
VL  - 175
DO  - 10.1530/EJE-16-0775
SP  - 551
EP  - 560
ER  - 
@article{
author = "Božić-Antić, Ivana and Ilić, Dušan and Bjekić-Macut, Jelica and Bogavac, Tamara and Vojnović-Milutinović, Danijela and Kastratovic-Kotlica, Biljana and Milić, Nataša and Stanojlović, Olivera and Andrić, Zoran and Macut, Djuro",
year = "2016",
abstract = "Objective: There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. Design: Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. Methods: In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. Results: All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. Conclusion: LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B.",
journal = "European Journal of Endocrinology",
title = "Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome",
number = "6",
volume = "175",
doi = "10.1530/EJE-16-0775",
pages = "551-560"
}
Božić-Antić, I., Ilić, D., Bjekić-Macut, J., Bogavac, T., Vojnović-Milutinović, D., Kastratovic-Kotlica, B., Milić, N., Stanojlović, O., Andrić, Z.,& Macut, D.. (2016). Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome. in European Journal of Endocrinology, 175(6), 551-560.
https://doi.org/10.1530/EJE-16-0775
Božić-Antić I, Ilić D, Bjekić-Macut J, Bogavac T, Vojnović-Milutinović D, Kastratovic-Kotlica B, Milić N, Stanojlović O, Andrić Z, Macut D. Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome. in European Journal of Endocrinology. 2016;175(6):551-560.
doi:10.1530/EJE-16-0775 .
Božić-Antić, Ivana, Ilić, Dušan, Bjekić-Macut, Jelica, Bogavac, Tamara, Vojnović-Milutinović, Danijela, Kastratovic-Kotlica, Biljana, Milić, Nataša, Stanojlović, Olivera, Andrić, Zoran, Macut, Djuro, "Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome" in European Journal of Endocrinology, 175, no. 6 (2016):551-560,
https://doi.org/10.1530/EJE-16-0775 . .
2
13
10
12

Cardiac fatty acid uptake and metabolism in the rat model of polycystic ovary syndrome

Tepavcevic, Snezana; Vojnović-Milutinović, Danijela; Macut, Djuro; Stojiljkovic, Mojca; Radovanović, Marina; Bozic-Antic, Ivana; Culafic, Tijana; Bjekić-Macut, Jelica; Matić, Gordana; Koricanac, Goran

(2015)

TY  - JOUR
AU  - Tepavcevic, Snezana
AU  - Vojnović-Milutinović, Danijela
AU  - Macut, Djuro
AU  - Stojiljkovic, Mojca
AU  - Radovanović, Marina
AU  - Bozic-Antic, Ivana
AU  - Culafic, Tijana
AU  - Bjekić-Macut, Jelica
AU  - Matić, Gordana
AU  - Koricanac, Goran
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1911
AB  - Polycystic ovary syndrome (PCOS) is associated with an altered plasma
   lipid profile and increased risk for cardiovascular diseases. We
   hypothesized that molecular mechanisms underlying cardiac pathology in
   PCOS involve changes in expression and subcellular localization of
   several key proteins involved in cardiac lipid transport and metabolism,
   such as fatty acid transporter CD36, lipin 1, peroxisome
   proliferator-activated receptor alpha (PPAR alpha), peroxisome
   proliferator-activated receptor gamma coactivator-1 (PGC1), and
   carnitine palmitoyltransferase 1 (CPT1). We used the animal model of
   PCOS obtained by treating female rats with dihydrotestosterone (DHT).
   Protein levels of CD36, lipin 1, PPAR alpha, PGC1, and antioxidative
   enzymes were assessed by Western blot in different cardiac cell
   compartments. Cardiac triglycerides (TG) and lipid peroxidation were
   also measured. The content of CD36 was decreased in both the cardiac
   plasma membranes and intracellular pool. On the other hand, total
   content of cardiac lipin 1 in DHT-treated rats was elevated, in contrast
   to decreased microsomal lipin 1 content. An increase in nuclear content
   of lipin 1 was observed together with elevation of nuclear PPAR alpha
   and PGC1, and an increase in CPT1 expression. However, lipid
   peroxidation was reduced in the heart, without alterations in
   antioxidative enzymes expression and cardiac TG content. The results
   indicate that treatment of female rats with DHT is accompanied by a
   decrease of fatty acid uptake and a reduction of lipid peroxidation in
   the heart. The observed elevation of lipin 1, PPAR alpha, PGC1, and CPT1
   expression suggests that cardiac fatty acid metabolism is shifted toward
   mitochondrial beta oxidation.
T2  - Endocrine
T1  - Cardiac fatty acid uptake and metabolism in the rat model of polycystic
 ovary syndrome
IS  - 1
VL  - 50
DO  - 10.1007/s12020-015-0558-1
SP  - 193
EP  - 201
ER  - 
@article{
author = "Tepavcevic, Snezana and Vojnović-Milutinović, Danijela and Macut, Djuro and Stojiljkovic, Mojca and Radovanović, Marina and Bozic-Antic, Ivana and Culafic, Tijana and Bjekić-Macut, Jelica and Matić, Gordana and Koricanac, Goran",
year = "2015",
abstract = "Polycystic ovary syndrome (PCOS) is associated with an altered plasma
   lipid profile and increased risk for cardiovascular diseases. We
   hypothesized that molecular mechanisms underlying cardiac pathology in
   PCOS involve changes in expression and subcellular localization of
   several key proteins involved in cardiac lipid transport and metabolism,
   such as fatty acid transporter CD36, lipin 1, peroxisome
   proliferator-activated receptor alpha (PPAR alpha), peroxisome
   proliferator-activated receptor gamma coactivator-1 (PGC1), and
   carnitine palmitoyltransferase 1 (CPT1). We used the animal model of
   PCOS obtained by treating female rats with dihydrotestosterone (DHT).
   Protein levels of CD36, lipin 1, PPAR alpha, PGC1, and antioxidative
   enzymes were assessed by Western blot in different cardiac cell
   compartments. Cardiac triglycerides (TG) and lipid peroxidation were
   also measured. The content of CD36 was decreased in both the cardiac
   plasma membranes and intracellular pool. On the other hand, total
   content of cardiac lipin 1 in DHT-treated rats was elevated, in contrast
   to decreased microsomal lipin 1 content. An increase in nuclear content
   of lipin 1 was observed together with elevation of nuclear PPAR alpha
   and PGC1, and an increase in CPT1 expression. However, lipid
   peroxidation was reduced in the heart, without alterations in
   antioxidative enzymes expression and cardiac TG content. The results
   indicate that treatment of female rats with DHT is accompanied by a
   decrease of fatty acid uptake and a reduction of lipid peroxidation in
   the heart. The observed elevation of lipin 1, PPAR alpha, PGC1, and CPT1
   expression suggests that cardiac fatty acid metabolism is shifted toward
   mitochondrial beta oxidation.",
journal = "Endocrine",
title = "Cardiac fatty acid uptake and metabolism in the rat model of polycystic
 ovary syndrome",
number = "1",
volume = "50",
doi = "10.1007/s12020-015-0558-1",
pages = "193-201"
}
Tepavcevic, S., Vojnović-Milutinović, D., Macut, D., Stojiljkovic, M., Radovanović, M., Bozic-Antic, I., Culafic, T., Bjekić-Macut, J., Matić, G.,& Koricanac, G.. (2015). Cardiac fatty acid uptake and metabolism in the rat model of polycystic
 ovary syndrome. in Endocrine, 50(1), 193-201.
https://doi.org/10.1007/s12020-015-0558-1
Tepavcevic S, Vojnović-Milutinović D, Macut D, Stojiljkovic M, Radovanović M, Bozic-Antic I, Culafic T, Bjekić-Macut J, Matić G, Koricanac G. Cardiac fatty acid uptake and metabolism in the rat model of polycystic
 ovary syndrome. in Endocrine. 2015;50(1):193-201.
doi:10.1007/s12020-015-0558-1 .
Tepavcevic, Snezana, Vojnović-Milutinović, Danijela, Macut, Djuro, Stojiljkovic, Mojca, Radovanović, Marina, Bozic-Antic, Ivana, Culafic, Tijana, Bjekić-Macut, Jelica, Matić, Gordana, Koricanac, Goran, "Cardiac fatty acid uptake and metabolism in the rat model of polycystic
 ovary syndrome" in Endocrine, 50, no. 1 (2015):193-201,
https://doi.org/10.1007/s12020-015-0558-1 . .
7
5
6

Possible involvement of glucocorticoids in 5 alpha-dihydrotestosterone-induced PCOS-like metabolic disturbances in the rat visceral adipose tissue

Radovanović, Marina; Macut, Đuro; Đorđević, Ana; Veličković, Nataša; Nestorović, Nataša; Bursać, Biljana; Božić-Antić, Ivana; Bjekić Macut, Jelica; Matić, Gordana; Vojnović-Milutinović, Danijela

(2015)

TY  - JOUR
AU  - Radovanović, Marina
AU  - Macut, Đuro
AU  - Đorđević, Ana
AU  - Veličković, Nataša
AU  - Nestorović, Nataša
AU  - Bursać, Biljana
AU  - Božić-Antić, Ivana
AU  - Bjekić Macut, Jelica
AU  - Matić, Gordana
AU  - Vojnović-Milutinović, Danijela
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2022
UR  - https://www.sciencedirect.com/science/article/pii/S0303720714002706?via%3Dihub#ac0010
AB  - Polycystic ovary syndrome (PCOS) is a reproductive and metabolic
   disorder characterized by hyperandrogenism, ovulatory dysfunction,
   visceral obesity and insulin resistance. We hypothesized that changes in
   glucocorticoid metabolism and signaling in the visceral adipose tissue
   may contribute to disturbances of lipid metabolism in the rat model of
   PCOS obtained by 5 alpha-dihydrotestosterone (DHT) treatment of
   prepubertal female Wistar rats. The results confirmed that DHT treatment
   caused anovulation, obesity and dyslipidemia. Enhanced glucocorticoid
   prereceptor metabolism, assessed by elevated intracellular
   corticosterone and increased 11 beta-hydroxysteroid dehydrogenase type 1
   mRNA and protein levels, was accompanied by glucocorticoid receptor (GR)
   nuclear accumulation. In concert with the increased expression of
   GR-regulated prolipogenic genes (lipin-1, sterol regulatory element
   binding protein 1, fatty acid synthase, phosphoenolpyruvate
   carboxykinase), histological analyses revealed hypertrophic adipocytes.
   The results suggest that glucocorticoids influence lipid metabolism in
   the visceral adipose tissue in the way that may contribute to
   pathogenesis of metabolic disturbances associated with PCOS. (C) 2014
   Elsevier Ireland Ltd. All rights reserved.
T2  - Molecular and Cellular Endocrinology
T1  - Possible involvement of glucocorticoids in 5
 alpha-dihydrotestosterone-induced PCOS-like metabolic disturbances in
 the rat visceral adipose tissue
IS  - C
VL  - 399
DO  - 10.1016/j.mce.2014.08.013
SP  - 22
EP  - 31
ER  - 
@article{
author = "Radovanović, Marina and Macut, Đuro and Đorđević, Ana and Veličković, Nataša and Nestorović, Nataša and Bursać, Biljana and Božić-Antić, Ivana and Bjekić Macut, Jelica and Matić, Gordana and Vojnović-Milutinović, Danijela",
year = "2015",
abstract = "Polycystic ovary syndrome (PCOS) is a reproductive and metabolic
   disorder characterized by hyperandrogenism, ovulatory dysfunction,
   visceral obesity and insulin resistance. We hypothesized that changes in
   glucocorticoid metabolism and signaling in the visceral adipose tissue
   may contribute to disturbances of lipid metabolism in the rat model of
   PCOS obtained by 5 alpha-dihydrotestosterone (DHT) treatment of
   prepubertal female Wistar rats. The results confirmed that DHT treatment
   caused anovulation, obesity and dyslipidemia. Enhanced glucocorticoid
   prereceptor metabolism, assessed by elevated intracellular
   corticosterone and increased 11 beta-hydroxysteroid dehydrogenase type 1
   mRNA and protein levels, was accompanied by glucocorticoid receptor (GR)
   nuclear accumulation. In concert with the increased expression of
   GR-regulated prolipogenic genes (lipin-1, sterol regulatory element
   binding protein 1, fatty acid synthase, phosphoenolpyruvate
   carboxykinase), histological analyses revealed hypertrophic adipocytes.
   The results suggest that glucocorticoids influence lipid metabolism in
   the visceral adipose tissue in the way that may contribute to
   pathogenesis of metabolic disturbances associated with PCOS. (C) 2014
   Elsevier Ireland Ltd. All rights reserved.",
journal = "Molecular and Cellular Endocrinology",
title = "Possible involvement of glucocorticoids in 5
 alpha-dihydrotestosterone-induced PCOS-like metabolic disturbances in
 the rat visceral adipose tissue",
number = "C",
volume = "399",
doi = "10.1016/j.mce.2014.08.013",
pages = "22-31"
}
Radovanović, M., Macut, Đ., Đorđević, A., Veličković, N., Nestorović, N., Bursać, B., Božić-Antić, I., Bjekić Macut, J., Matić, G.,& Vojnović-Milutinović, D.. (2015). Possible involvement of glucocorticoids in 5
 alpha-dihydrotestosterone-induced PCOS-like metabolic disturbances in
 the rat visceral adipose tissue. in Molecular and Cellular Endocrinology, 399(C), 22-31.
https://doi.org/10.1016/j.mce.2014.08.013
Radovanović M, Macut Đ, Đorđević A, Veličković N, Nestorović N, Bursać B, Božić-Antić I, Bjekić Macut J, Matić G, Vojnović-Milutinović D. Possible involvement of glucocorticoids in 5
 alpha-dihydrotestosterone-induced PCOS-like metabolic disturbances in
 the rat visceral adipose tissue. in Molecular and Cellular Endocrinology. 2015;399(C):22-31.
doi:10.1016/j.mce.2014.08.013 .
Radovanović, Marina, Macut, Đuro, Đorđević, Ana, Veličković, Nataša, Nestorović, Nataša, Bursać, Biljana, Božić-Antić, Ivana, Bjekić Macut, Jelica, Matić, Gordana, Vojnović-Milutinović, Danijela, "Possible involvement of glucocorticoids in 5
 alpha-dihydrotestosterone-induced PCOS-like metabolic disturbances in
 the rat visceral adipose tissue" in Molecular and Cellular Endocrinology, 399, no. C (2015):22-31,
https://doi.org/10.1016/j.mce.2014.08.013 . .
25
16
25

The influence of combined oral contraceptives containing drospirenone on hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome

Macut, Djuro; Bozic-Antic, Ivana; Brkljačić, Jelena; Topalovic, Vladanka; Macut, Jelica Bjekic; Panidis, Dimitrios; Kotlica, Biljana Kastratovic; Papadakis, Efstathios; Matić, Gordana; Vojnović-Milutinović, Danijela

(2015)

TY  - JOUR
AU  - Macut, Djuro
AU  - Bozic-Antic, Ivana
AU  - Brkljačić, Jelena
AU  - Topalovic, Vladanka
AU  - Macut, Jelica Bjekic
AU  - Panidis, Dimitrios
AU  - Kotlica, Biljana Kastratovic
AU  - Papadakis, Efstathios
AU  - Matić, Gordana
AU  - Vojnović-Milutinović, Danijela
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2069
AB  - OBJECTIVE: Most women with PCOS have increased adrenal androgen
   production, enhanced peripheral metabolism of cortisol and elevation in
   urinary excretion of its metabolites. Increased cortisol clearance in
   PCOS is followed by a compensatory overdrive of the
   hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that
   oral contraceptives containing ethinylestradiol and drospirenone
   (EE-DRSP) could modulate glucocorticoid receptor (GR) expression and
   function and thus affect HPA axis activity in PCOS patients. DESIGN: We
   analyzed 12 women with PCOS (age 24.17 +/- 4.88 years; body mass index
   22.05 +/- 3.97 kg/m(2)) treated for 12 months with EE-DRSP and 20 BMI
   matched controls. In all subjects testosterone, dehydroepiandrosterone
   sulfate (DHEAS), sex hormone binding globulin (SHBG), cortisol (basal
   and after dexamethasone), concentrations of GR protein, phospo-GR211
   protein, number of GR per cell (B-max) and its equilibrium dissociation
   constant (K-D) were measured. RESULTS: Before treatment, increased
   concentrations of testosterone and DHEAS (p<0.001, respectively),
   unaltered basal cortisol and an increased sensitivity (p<0.05) of the
   HPA axis to dexamethasone were observed in PCOS women in comparison to
   controls. After treatment, testosterone (p<0.01), DHEAS (p<0.05) and
   cortisol suppression after dexamethasone (p<0.01) were decreased in PCOS
   women. There were no changes in GR protein concentration, GR
   phosphorylation nor in the receptor functional parameters B-max and K-D
   in women with PCOS before and after the therapy, and in comparison to
   controls. CONCLUSIONS: Prolonged treatment with EE-DRSP in PCOS women
   decreased serum androgens and increased cortisol in the presence of
   decreased sensitivity of the HPA axis and did not exert changes in GR
   expression and function.
T2  - Hormones-International Journal of Endocrinology and Metabolism
T1  - The influence of combined oral contraceptives containing drospirenone on
 hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid
 receptor expression and function in women with polycystic ovary syndrome
IS  - 1
VL  - 14
SP  - 109
EP  - 117
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_2069
ER  - 
@article{
author = "Macut, Djuro and Bozic-Antic, Ivana and Brkljačić, Jelena and Topalovic, Vladanka and Macut, Jelica Bjekic and Panidis, Dimitrios and Kotlica, Biljana Kastratovic and Papadakis, Efstathios and Matić, Gordana and Vojnović-Milutinović, Danijela",
year = "2015",
abstract = "OBJECTIVE: Most women with PCOS have increased adrenal androgen
   production, enhanced peripheral metabolism of cortisol and elevation in
   urinary excretion of its metabolites. Increased cortisol clearance in
   PCOS is followed by a compensatory overdrive of the
   hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that
   oral contraceptives containing ethinylestradiol and drospirenone
   (EE-DRSP) could modulate glucocorticoid receptor (GR) expression and
   function and thus affect HPA axis activity in PCOS patients. DESIGN: We
   analyzed 12 women with PCOS (age 24.17 +/- 4.88 years; body mass index
   22.05 +/- 3.97 kg/m(2)) treated for 12 months with EE-DRSP and 20 BMI
   matched controls. In all subjects testosterone, dehydroepiandrosterone
   sulfate (DHEAS), sex hormone binding globulin (SHBG), cortisol (basal
   and after dexamethasone), concentrations of GR protein, phospo-GR211
   protein, number of GR per cell (B-max) and its equilibrium dissociation
   constant (K-D) were measured. RESULTS: Before treatment, increased
   concentrations of testosterone and DHEAS (p<0.001, respectively),
   unaltered basal cortisol and an increased sensitivity (p<0.05) of the
   HPA axis to dexamethasone were observed in PCOS women in comparison to
   controls. After treatment, testosterone (p<0.01), DHEAS (p<0.05) and
   cortisol suppression after dexamethasone (p<0.01) were decreased in PCOS
   women. There were no changes in GR protein concentration, GR
   phosphorylation nor in the receptor functional parameters B-max and K-D
   in women with PCOS before and after the therapy, and in comparison to
   controls. CONCLUSIONS: Prolonged treatment with EE-DRSP in PCOS women
   decreased serum androgens and increased cortisol in the presence of
   decreased sensitivity of the HPA axis and did not exert changes in GR
   expression and function.",
journal = "Hormones-International Journal of Endocrinology and Metabolism",
title = "The influence of combined oral contraceptives containing drospirenone on
 hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid
 receptor expression and function in women with polycystic ovary syndrome",
number = "1",
volume = "14",
pages = "109-117",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2069"
}
Macut, D., Bozic-Antic, I., Brkljačić, J., Topalovic, V., Macut, J. B., Panidis, D., Kotlica, B. K., Papadakis, E., Matić, G.,& Vojnović-Milutinović, D.. (2015). The influence of combined oral contraceptives containing drospirenone on
 hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid
 receptor expression and function in women with polycystic ovary syndrome. in Hormones-International Journal of Endocrinology and Metabolism, 14(1), 109-117.
https://hdl.handle.net/21.15107/rcub_ibiss_2069
Macut D, Bozic-Antic I, Brkljačić J, Topalovic V, Macut JB, Panidis D, Kotlica BK, Papadakis E, Matić G, Vojnović-Milutinović D. The influence of combined oral contraceptives containing drospirenone on
 hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid
 receptor expression and function in women with polycystic ovary syndrome. in Hormones-International Journal of Endocrinology and Metabolism. 2015;14(1):109-117.
https://hdl.handle.net/21.15107/rcub_ibiss_2069 .
Macut, Djuro, Bozic-Antic, Ivana, Brkljačić, Jelena, Topalovic, Vladanka, Macut, Jelica Bjekic, Panidis, Dimitrios, Kotlica, Biljana Kastratovic, Papadakis, Efstathios, Matić, Gordana, Vojnović-Milutinović, Danijela, "The influence of combined oral contraceptives containing drospirenone on
 hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid
 receptor expression and function in women with polycystic ovary syndrome" in Hormones-International Journal of Endocrinology and Metabolism, 14, no. 1 (2015):109-117,
https://hdl.handle.net/21.15107/rcub_ibiss_2069 .
8

Predictors of Subclinical Cardiovascular Disease in Women with Polycystic Ovary Syndrome: Interrelationship of Dyslipidemia and Arterial Blood Pressure

Macut, Đuro; Bačević, Marina; Božić-Antić, Ivana; Bjekić-Macut, Jelica; Civcic, Milorad; Erceg, Snježana; Vojnović-Milutinović, Danijela; Stanojlović, Olivera; Andrić, Zoran; Kastratović-Kotlica, Biljana; Sukilović, Tijana

(2015)

TY  - JOUR
AU  - Macut, Đuro
AU  - Bačević, Marina
AU  - Božić-Antić, Ivana
AU  - Bjekić-Macut, Jelica
AU  - Civcic, Milorad
AU  - Erceg, Snježana
AU  - Vojnović-Milutinović, Danijela
AU  - Stanojlović, Olivera
AU  - Andrić, Zoran
AU  - Kastratović-Kotlica, Biljana
AU  - Sukilović, Tijana
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2071
AB  - Background. Women with polycystic ovary syndrome (PCOS) could develop
   subclinical atherosclerosis during life. Purpose. To analyze
   cardiovascular risk (CVR) factors and their relation to clinical markers
   of cardiovascular disease (CVD) in respect to their age. Material and
   Methods. One hundred women with PCOS (26.32 +/- 5.26 years, BMI: 24.98
   +/- 6.38 kg/m(2)) were compared to 50 respective controls. In all
   subjects, total cholesterol (TC), HDL-C, LDL-C, triglycerides, TC/HDL-C
   and TG/HDL-C ratios, glucose, insulin and HOMA index, waist-to-hip ratio
   (WHR), systolic and diastolic blood pressure (SBP and DBP, resp.), and
   carotid intima-media thickness (CIMT) were analyzed in respect to their
   age and level of androgens. Results. PCOS over 30 years had higher WHR
   (P = 0.008), SBP (P < 0.001), DBP (P < 0.001), TC (P = 0.028), HDL-C (P
   = 0.028), LDL-C (P = 0.045), triglycerides (P < 0.001), TC/HDL-C (P <
   0.001), and triglycerides/HDL-C (P < 0.001) and had more prevalent
   hypertension and pronounced CIMT on common carotid arteries even after
   adjustment for BMI (P = 0.005 and 0.036, resp.). TC/ HDL-C and TG/HDL-C
   were higher in PCOS with the highest quintile of FAI in comparison to
   those with lower FAI (P = 0.045 and 0.034, resp.). Conclusions. PCOS
   women older than 30 years irrespective of BMI have the potential for
   early atherosclerosismirrored through the elevated lipids/lipid ratios
   and through changes in blood pressure.
T2  - International Journal of Endocrinology
T1  - Predictors of Subclinical Cardiovascular Disease in Women with
 Polycystic Ovary Syndrome: Interrelationship of Dyslipidemia and
 Arterial Blood Pressure
IS  - 812610
DO  - 10.1155/2015/812610
ER  - 
@article{
author = "Macut, Đuro and Bačević, Marina and Božić-Antić, Ivana and Bjekić-Macut, Jelica and Civcic, Milorad and Erceg, Snježana and Vojnović-Milutinović, Danijela and Stanojlović, Olivera and Andrić, Zoran and Kastratović-Kotlica, Biljana and Sukilović, Tijana",
year = "2015",
abstract = "Background. Women with polycystic ovary syndrome (PCOS) could develop
   subclinical atherosclerosis during life. Purpose. To analyze
   cardiovascular risk (CVR) factors and their relation to clinical markers
   of cardiovascular disease (CVD) in respect to their age. Material and
   Methods. One hundred women with PCOS (26.32 +/- 5.26 years, BMI: 24.98
   +/- 6.38 kg/m(2)) were compared to 50 respective controls. In all
   subjects, total cholesterol (TC), HDL-C, LDL-C, triglycerides, TC/HDL-C
   and TG/HDL-C ratios, glucose, insulin and HOMA index, waist-to-hip ratio
   (WHR), systolic and diastolic blood pressure (SBP and DBP, resp.), and
   carotid intima-media thickness (CIMT) were analyzed in respect to their
   age and level of androgens. Results. PCOS over 30 years had higher WHR
   (P = 0.008), SBP (P < 0.001), DBP (P < 0.001), TC (P = 0.028), HDL-C (P
   = 0.028), LDL-C (P = 0.045), triglycerides (P < 0.001), TC/HDL-C (P <
   0.001), and triglycerides/HDL-C (P < 0.001) and had more prevalent
   hypertension and pronounced CIMT on common carotid arteries even after
   adjustment for BMI (P = 0.005 and 0.036, resp.). TC/ HDL-C and TG/HDL-C
   were higher in PCOS with the highest quintile of FAI in comparison to
   those with lower FAI (P = 0.045 and 0.034, resp.). Conclusions. PCOS
   women older than 30 years irrespective of BMI have the potential for
   early atherosclerosismirrored through the elevated lipids/lipid ratios
   and through changes in blood pressure.",
journal = "International Journal of Endocrinology",
title = "Predictors of Subclinical Cardiovascular Disease in Women with
 Polycystic Ovary Syndrome: Interrelationship of Dyslipidemia and
 Arterial Blood Pressure",
number = "812610",
doi = "10.1155/2015/812610"
}
Macut, Đ., Bačević, M., Božić-Antić, I., Bjekić-Macut, J., Civcic, M., Erceg, S., Vojnović-Milutinović, D., Stanojlović, O., Andrić, Z., Kastratović-Kotlica, B.,& Sukilović, T.. (2015). Predictors of Subclinical Cardiovascular Disease in Women with
 Polycystic Ovary Syndrome: Interrelationship of Dyslipidemia and
 Arterial Blood Pressure. in International Journal of Endocrinology(812610).
https://doi.org/10.1155/2015/812610
Macut Đ, Bačević M, Božić-Antić I, Bjekić-Macut J, Civcic M, Erceg S, Vojnović-Milutinović D, Stanojlović O, Andrić Z, Kastratović-Kotlica B, Sukilović T. Predictors of Subclinical Cardiovascular Disease in Women with
 Polycystic Ovary Syndrome: Interrelationship of Dyslipidemia and
 Arterial Blood Pressure. in International Journal of Endocrinology. 2015;(812610).
doi:10.1155/2015/812610 .
Macut, Đuro, Bačević, Marina, Božić-Antić, Ivana, Bjekić-Macut, Jelica, Civcic, Milorad, Erceg, Snježana, Vojnović-Milutinović, Danijela, Stanojlović, Olivera, Andrić, Zoran, Kastratović-Kotlica, Biljana, Sukilović, Tijana, "Predictors of Subclinical Cardiovascular Disease in Women with
 Polycystic Ovary Syndrome: Interrelationship of Dyslipidemia and
 Arterial Blood Pressure" in International Journal of Endocrinology, no. 812610 (2015),
https://doi.org/10.1155/2015/812610 . .
23
20
27

Dihydrotestosterone deteriorates cardiac insulin signaling and glucose transport in the rat model of polycystic ovary syndrome

Tepavcevic, Snezana; Vojnović-Milutinović, Danijela; Macut, Djuro; Zakula, Zorica; Radovanović, Marina; Bozic-Antic, Ivana; Romic, Snjezana; Bjekić-Macut, Jelica; Matić, Gordana; Koricanac, Goran

(2014)

TY  - JOUR
AU  - Tepavcevic, Snezana
AU  - Vojnović-Milutinović, Danijela
AU  - Macut, Djuro
AU  - Zakula, Zorica
AU  - Radovanović, Marina
AU  - Bozic-Antic, Ivana
AU  - Romic, Snjezana
AU  - Bjekić-Macut, Jelica
AU  - Matić, Gordana
AU  - Koricanac, Goran
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2217
AB  - It is supposed that women with polycystic ovary syndrome (PCOS) are
   prone to develop cardiovascular disease as a consequence of multiple
   risk factors that are mostly related to the state of insulin resistance
   and consequent hyperinsulinemia. In the present study, we evaluated
   insulin signaling and glucose transporters (GLUT) in cardiac cells of
   dihydrotestosterone (DHT) treated female rats as an animal model of
   PCOS. Expression of proteins involved in cardiac insulin signaling
   pathways and glucose transporters, as well as their phosphorylation or
   intracellular localization were studied by Western blot analysis in
   DHT-treated and control rats. Treatment with DHT resulted in increased
   body mass, absolute mass of the heart, elevated plasma insulin
   concentration, dyslipidemia and insulin resistance. At the molecular
   level, DHT treatment did not change protein expression of cardiac
   insulin receptor and insulin receptor substrate 1, while phosphorylation
   of the substrate at serine 307 was increased. Unexpectedly, although
   expression of downstream Akt kinase and its phosphorylation at threonine
   308 were not altered, phosphoiylation of Akt at serine 473 was increased
   in the heart of DHT-treated rats. In contrast, expression and
   phosphorylation of extracellular signal regulated kinases 1/2 were
   decreased. Plasma membrane contents of GLUT1 and GLUT4 were decreased,
   as well as the expression of GLUT4 in cardiac cells at the end of
   androgen treatment. The obtained results provide evidence for
   alterations in expression and especially in functional characteristics
   of insulin signaling molecules and glucose transporters in the heart of
   DHT-treated rats with PCOS, indicating impaired cardiac insulin action.
   (c) 2014 Elsevier Ltd. All rights reserved.
T2  - Journal of Steroid Biochemistry and Molecular Biology
T1  - Dihydrotestosterone deteriorates cardiac insulin signaling and glucose
 transport in the rat model of polycystic ovary syndrome
VL  - 141
DO  - 10.1016/j.jsbmb.2014.01.006
SP  - 71
EP  - 76
ER  - 
@article{
author = "Tepavcevic, Snezana and Vojnović-Milutinović, Danijela and Macut, Djuro and Zakula, Zorica and Radovanović, Marina and Bozic-Antic, Ivana and Romic, Snjezana and Bjekić-Macut, Jelica and Matić, Gordana and Koricanac, Goran",
year = "2014",
abstract = "It is supposed that women with polycystic ovary syndrome (PCOS) are
   prone to develop cardiovascular disease as a consequence of multiple
   risk factors that are mostly related to the state of insulin resistance
   and consequent hyperinsulinemia. In the present study, we evaluated
   insulin signaling and glucose transporters (GLUT) in cardiac cells of
   dihydrotestosterone (DHT) treated female rats as an animal model of
   PCOS. Expression of proteins involved in cardiac insulin signaling
   pathways and glucose transporters, as well as their phosphorylation or
   intracellular localization were studied by Western blot analysis in
   DHT-treated and control rats. Treatment with DHT resulted in increased
   body mass, absolute mass of the heart, elevated plasma insulin
   concentration, dyslipidemia and insulin resistance. At the molecular
   level, DHT treatment did not change protein expression of cardiac
   insulin receptor and insulin receptor substrate 1, while phosphorylation
   of the substrate at serine 307 was increased. Unexpectedly, although
   expression of downstream Akt kinase and its phosphorylation at threonine
   308 were not altered, phosphoiylation of Akt at serine 473 was increased
   in the heart of DHT-treated rats. In contrast, expression and
   phosphorylation of extracellular signal regulated kinases 1/2 were
   decreased. Plasma membrane contents of GLUT1 and GLUT4 were decreased,
   as well as the expression of GLUT4 in cardiac cells at the end of
   androgen treatment. The obtained results provide evidence for
   alterations in expression and especially in functional characteristics
   of insulin signaling molecules and glucose transporters in the heart of
   DHT-treated rats with PCOS, indicating impaired cardiac insulin action.
   (c) 2014 Elsevier Ltd. All rights reserved.",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
title = "Dihydrotestosterone deteriorates cardiac insulin signaling and glucose
 transport in the rat model of polycystic ovary syndrome",
volume = "141",
doi = "10.1016/j.jsbmb.2014.01.006",
pages = "71-76"
}
Tepavcevic, S., Vojnović-Milutinović, D., Macut, D., Zakula, Z., Radovanović, M., Bozic-Antic, I., Romic, S., Bjekić-Macut, J., Matić, G.,& Koricanac, G.. (2014). Dihydrotestosterone deteriorates cardiac insulin signaling and glucose
 transport in the rat model of polycystic ovary syndrome. in Journal of Steroid Biochemistry and Molecular Biology, 141, 71-76.
https://doi.org/10.1016/j.jsbmb.2014.01.006
Tepavcevic S, Vojnović-Milutinović D, Macut D, Zakula Z, Radovanović M, Bozic-Antic I, Romic S, Bjekić-Macut J, Matić G, Koricanac G. Dihydrotestosterone deteriorates cardiac insulin signaling and glucose
 transport in the rat model of polycystic ovary syndrome. in Journal of Steroid Biochemistry and Molecular Biology. 2014;141:71-76.
doi:10.1016/j.jsbmb.2014.01.006 .
Tepavcevic, Snezana, Vojnović-Milutinović, Danijela, Macut, Djuro, Zakula, Zorica, Radovanović, Marina, Bozic-Antic, Ivana, Romic, Snjezana, Bjekić-Macut, Jelica, Matić, Gordana, Koricanac, Goran, "Dihydrotestosterone deteriorates cardiac insulin signaling and glucose
 transport in the rat model of polycystic ovary syndrome" in Journal of Steroid Biochemistry and Molecular Biology, 141 (2014):71-76,
https://doi.org/10.1016/j.jsbmb.2014.01.006 . .
13
12
13

Hypoxanthine Guanine Phosphoribosyl Transferase Is the Most Stable Reference Gene for Gene Expression Analysis by Quantitative PCR in Peripheral Blood Mononuclear Cells from Women with the Polycystic Ovary Syndrome

Vojnović-Milutinović, Danijela; Macut, Djuro; Bozic-Antic, Ivana; Macut, Jelica Bjekic; Radovanović, Marina; Matić, Gordana; Brkljačić, Jelena

(2014)

TY  - JOUR
AU  - Vojnović-Milutinović, Danijela
AU  - Macut, Djuro
AU  - Bozic-Antic, Ivana
AU  - Macut, Jelica Bjekic
AU  - Radovanović, Marina
AU  - Matić, Gordana
AU  - Brkljačić, Jelena
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2157
AB  - Background: The polycystic ovary syndrome (PCOS) is a frequent endocrine
   disorder that affects women of reproductive age. As the syndrome is
   strongly associated with obesity, it is of interest to examine the gene
   expression differences that accompany its development and the associated
   metabolic disturbances. Real-time RT PCR is a standard method for
   studying changes in gene expression. However, to obtain accurate and
   reliable results, validation of reference genes is obligatory. The aim
   of this study was to identify a suitable reference for the normalization
   of gene expression in peripheral blood mononuclear cells (PBMCs) from
   obese and normal-weight women with PCOS.
   Methods: The expression stability of four potential reference genes:
   hypoxanthine guanine phosphoribosyl transferase 1 (HPRT), beta-actin
   (BA), beta(2)-microglobulin (B2M) and glyceraldehyde-3-phosphate
   dehydrogenase (GAPDH), was assessed in PBMCs from healthy women, and
   from normal-weight and obese women with PCOS. The variability in the
   expression of potential reference genes was analyzed by the TaqMan
   real-time RT PCR method, using GeNorm and Norm Finder software packages.
   Results: Direct comparison of cycle threshold (Ct) values showed
   inter-individual variations for all validated genes, the Ct values of
   HPRT being less variable than those of BA, GAPDH and B2M. Both software
   packages pointed to HPRT as the most steadily expressed gene in the
   PBMCs of women with PCOS and healthy controls.
   Conclusions: Cross-validation of the expression stability of four
   potential reference genes identified HPRT as the most stable reference,
   suitable for further investigations of gene expression in PBMCs from
   women with PCOS.
T2  - Journal of Medical Biochemistry
T1  - Hypoxanthine Guanine Phosphoribosyl Transferase Is the Most Stable Reference Gene for Gene Expression Analysis by Quantitative PCR in Peripheral Blood Mononuclear Cells from Women with the Polycystic Ovary Syndrome
IS  - 4
VL  - 33
DO  - 10.2478/jomb-2014-0029
SP  - 356
EP  - 363
ER  - 
@article{
author = "Vojnović-Milutinović, Danijela and Macut, Djuro and Bozic-Antic, Ivana and Macut, Jelica Bjekic and Radovanović, Marina and Matić, Gordana and Brkljačić, Jelena",
year = "2014",
abstract = "Background: The polycystic ovary syndrome (PCOS) is a frequent endocrine
   disorder that affects women of reproductive age. As the syndrome is
   strongly associated with obesity, it is of interest to examine the gene
   expression differences that accompany its development and the associated
   metabolic disturbances. Real-time RT PCR is a standard method for
   studying changes in gene expression. However, to obtain accurate and
   reliable results, validation of reference genes is obligatory. The aim
   of this study was to identify a suitable reference for the normalization
   of gene expression in peripheral blood mononuclear cells (PBMCs) from
   obese and normal-weight women with PCOS.
   Methods: The expression stability of four potential reference genes:
   hypoxanthine guanine phosphoribosyl transferase 1 (HPRT), beta-actin
   (BA), beta(2)-microglobulin (B2M) and glyceraldehyde-3-phosphate
   dehydrogenase (GAPDH), was assessed in PBMCs from healthy women, and
   from normal-weight and obese women with PCOS. The variability in the
   expression of potential reference genes was analyzed by the TaqMan
   real-time RT PCR method, using GeNorm and Norm Finder software packages.
   Results: Direct comparison of cycle threshold (Ct) values showed
   inter-individual variations for all validated genes, the Ct values of
   HPRT being less variable than those of BA, GAPDH and B2M. Both software
   packages pointed to HPRT as the most steadily expressed gene in the
   PBMCs of women with PCOS and healthy controls.
   Conclusions: Cross-validation of the expression stability of four
   potential reference genes identified HPRT as the most stable reference,
   suitable for further investigations of gene expression in PBMCs from
   women with PCOS.",
journal = "Journal of Medical Biochemistry",
title = "Hypoxanthine Guanine Phosphoribosyl Transferase Is the Most Stable Reference Gene for Gene Expression Analysis by Quantitative PCR in Peripheral Blood Mononuclear Cells from Women with the Polycystic Ovary Syndrome",
number = "4",
volume = "33",
doi = "10.2478/jomb-2014-0029",
pages = "356-363"
}
Vojnović-Milutinović, D., Macut, D., Bozic-Antic, I., Macut, J. B., Radovanović, M., Matić, G.,& Brkljačić, J.. (2014). Hypoxanthine Guanine Phosphoribosyl Transferase Is the Most Stable Reference Gene for Gene Expression Analysis by Quantitative PCR in Peripheral Blood Mononuclear Cells from Women with the Polycystic Ovary Syndrome. in Journal of Medical Biochemistry, 33(4), 356-363.
https://doi.org/10.2478/jomb-2014-0029
Vojnović-Milutinović D, Macut D, Bozic-Antic I, Macut JB, Radovanović M, Matić G, Brkljačić J. Hypoxanthine Guanine Phosphoribosyl Transferase Is the Most Stable Reference Gene for Gene Expression Analysis by Quantitative PCR in Peripheral Blood Mononuclear Cells from Women with the Polycystic Ovary Syndrome. in Journal of Medical Biochemistry. 2014;33(4):356-363.
doi:10.2478/jomb-2014-0029 .
Vojnović-Milutinović, Danijela, Macut, Djuro, Bozic-Antic, Ivana, Macut, Jelica Bjekic, Radovanović, Marina, Matić, Gordana, Brkljačić, Jelena, "Hypoxanthine Guanine Phosphoribosyl Transferase Is the Most Stable Reference Gene for Gene Expression Analysis by Quantitative PCR in Peripheral Blood Mononuclear Cells from Women with the Polycystic Ovary Syndrome" in Journal of Medical Biochemistry, 33, no. 4 (2014):356-363,
https://doi.org/10.2478/jomb-2014-0029 . .
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