TY  - JOUR
AU  - Bursać, Biljana
AU  - Bellachioma, Luisa
AU  - Gligorovska, Ljupka
AU  - Jovanović, Mirna
AU  - Teofilović, Ana
AU  - Vratarić, Miloš
AU  - Vojnović Milutinović, Danijela
AU  - Albacete, Alfonso
AU  - Martínez-Melgarejo, Purificación A
AU  - Morresi, Camilla
AU  - Damiani, Elisabetta
AU  - Bacchetti, Tiziana
AU  - Đorđević, Ana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6533
AB  - Obesity is a pressing problem worldwide for which standard therapeutic strategies have limited effectiveness. The use of natural products seems to be a promising approach to alleviate obesity and its associated complications. The tepals of Crocus sativus plant, usually wasted in saffron production, are an unexplored source of bioactive compounds. Our aim was to elucidate the mechanisms of Crocus sativus (Cr) tepals extract in obesity by investigating its effects on adipocyte differentiation, visceral (VAT) and subcutaneous (SAT) adipose tissue hypertrophy, and lipid metabolism in an animal model of diet-induced obesity. To this end, mouse 3T3-F442A preadipocytes were treated with Cr tepals extract and the expression of adipocyte differentiation genes was determined. Caloric intake, body mass, triglycerides, systemic insulin sensitivity, histology, insulin signaling and lipid metabolism in VAT and SAT were analyzed in mice fed a 60% fat diet for 14 weeks and treated orally with Cr tepals extract during the last 5 weeks of the diet. We demonstrated for the first time that Cr tepals extract inhibits adipocyte differentiation in vitro. The animal model confirmed that oral treatment with Cr tepals extract results in weight loss, improved systemic insulin sensitivity, lower triglycerides, and improved lipid peroxidation. The suppressive effect of Cr tepals extract on adipocyte hypertrophy and inflammation was observed only in SAT, which, together with preserved SAT insulin signaling, most likely contributed to improved systemic insulin sensitivity. Our results suggest the functionality of SAT as a possible target for the treatment of obesity and its complications.
PB  - Hoboken: John Wiley and Sons
T2  - BioFactors
T1  - Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet
DO  - 10.1002/biof.2043
ER  - 

@article{
author = "Bursać, Biljana and Bellachioma, Luisa and Gligorovska, Ljupka and Jovanović, Mirna and Teofilović, Ana and Vratarić, Miloš and Vojnović Milutinović, Danijela and Albacete, Alfonso and Martínez-Melgarejo, Purificación A and Morresi, Camilla and Damiani, Elisabetta and Bacchetti, Tiziana and Đorđević, Ana",
year = "2024",
abstract = "Obesity is a pressing problem worldwide for which standard therapeutic strategies have limited effectiveness. The use of natural products seems to be a promising approach to alleviate obesity and its associated complications. The tepals of Crocus sativus plant, usually wasted in saffron production, are an unexplored source of bioactive compounds. Our aim was to elucidate the mechanisms of Crocus sativus (Cr) tepals extract in obesity by investigating its effects on adipocyte differentiation, visceral (VAT) and subcutaneous (SAT) adipose tissue hypertrophy, and lipid metabolism in an animal model of diet-induced obesity. To this end, mouse 3T3-F442A preadipocytes were treated with Cr tepals extract and the expression of adipocyte differentiation genes was determined. Caloric intake, body mass, triglycerides, systemic insulin sensitivity, histology, insulin signaling and lipid metabolism in VAT and SAT were analyzed in mice fed a 60% fat diet for 14 weeks and treated orally with Cr tepals extract during the last 5 weeks of the diet. We demonstrated for the first time that Cr tepals extract inhibits adipocyte differentiation in vitro. The animal model confirmed that oral treatment with Cr tepals extract results in weight loss, improved systemic insulin sensitivity, lower triglycerides, and improved lipid peroxidation. The suppressive effect of Cr tepals extract on adipocyte hypertrophy and inflammation was observed only in SAT, which, together with preserved SAT insulin signaling, most likely contributed to improved systemic insulin sensitivity. Our results suggest the functionality of SAT as a possible target for the treatment of obesity and its complications.",
publisher = "Hoboken: John Wiley and Sons",
journal = "BioFactors",
title = "Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet",
doi = "10.1002/biof.2043"
}

Bursać, B., Bellachioma, L., Gligorovska, L., Jovanović, M., Teofilović, A., Vratarić, M., Vojnović Milutinović, D., Albacete, A., Martínez-Melgarejo, P. A., Morresi, C., Damiani, E., Bacchetti, T.,& Đorđević, A.. (2024). Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet. in BioFactors
Hoboken: John Wiley and Sons..
https://doi.org/10.1002/biof.2043

Bursać B, Bellachioma L, Gligorovska L, Jovanović M, Teofilović A, Vratarić M, Vojnović Milutinović D, Albacete A, Martínez-Melgarejo PA, Morresi C, Damiani E, Bacchetti T, Đorđević A. Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet. in BioFactors. 2024;.
doi:10.1002/biof.2043 .

Bursać, Biljana, Bellachioma, Luisa, Gligorovska, Ljupka, Jovanović, Mirna, Teofilović, Ana, Vratarić, Miloš, Vojnović Milutinović, Danijela, Albacete, Alfonso, Martínez-Melgarejo, Purificación A, Morresi, Camilla, Damiani, Elisabetta, Bacchetti, Tiziana, Đorđević, Ana, "Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet" in BioFactors (2024),
https://doi.org/10.1002/biof.2043 . .

TY  - JOUR
AU  - Bursać, Biljana
AU  - Bellachioma, Luisa
AU  - Gligorovska, Ljupka
AU  - Jovanović, Mirna
AU  - Teofilović, Ana
AU  - Vratarić, Miloš
AU  - Vojnović Milutinović, Danijela
AU  - Albacete, Alfonso
AU  - Martínez-Melgarejo, Purificación A
AU  - Morresi, Camilla
AU  - Damiani, Elisabetta
AU  - Bacchetti, Tiziana
AU  - Đorđević, Ana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6532
AB  - Obesity is a pressing problem worldwide for which standard therapeutic strategies have limited effectiveness. The use of natural products seems to be a promising approach to alleviate obesity and its associated complications. The tepals of Crocus sativus plant, usually wasted in saffron production, are an unexplored source of bioactive compounds. Our aim was to elucidate the mechanisms of Crocus sativus (Cr) tepals extract in obesity by investigating its effects on adipocyte differentiation, visceral (VAT) and subcutaneous (SAT) adipose tissue hypertrophy, and lipid metabolism in an animal model of diet-induced obesity. To this end, mouse 3T3-F442A preadipocytes were treated with Cr tepals extract and the expression of adipocyte differentiation genes was determined. Caloric intake, body mass, triglycerides, systemic insulin sensitivity, histology, insulin signaling and lipid metabolism in VAT and SAT were analyzed in mice fed a 60% fat diet for 14 weeks and treated orally with Cr tepals extract during the last 5 weeks of the diet. We demonstrated for the first time that Cr tepals extract inhibits adipocyte differentiation in vitro. The animal model confirmed that oral treatment with Cr tepals extract results in weight loss, improved systemic insulin sensitivity, lower triglycerides, and improved lipid peroxidation. The suppressive effect of Cr tepals extract on adipocyte hypertrophy and inflammation was observed only in SAT, which, together with preserved SAT insulin signaling, most likely contributed to improved systemic insulin sensitivity. Our results suggest the functionality of SAT as a possible target for the treatment of obesity and its complications.
PB  - Hoboken: John Wiley and Sons
T2  - BioFactors
T1  - Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet
DO  - 10.1002/biof.2043
ER  - 

@article{
author = "Bursać, Biljana and Bellachioma, Luisa and Gligorovska, Ljupka and Jovanović, Mirna and Teofilović, Ana and Vratarić, Miloš and Vojnović Milutinović, Danijela and Albacete, Alfonso and Martínez-Melgarejo, Purificación A and Morresi, Camilla and Damiani, Elisabetta and Bacchetti, Tiziana and Đorđević, Ana",
year = "2024",
abstract = "Obesity is a pressing problem worldwide for which standard therapeutic strategies have limited effectiveness. The use of natural products seems to be a promising approach to alleviate obesity and its associated complications. The tepals of Crocus sativus plant, usually wasted in saffron production, are an unexplored source of bioactive compounds. Our aim was to elucidate the mechanisms of Crocus sativus (Cr) tepals extract in obesity by investigating its effects on adipocyte differentiation, visceral (VAT) and subcutaneous (SAT) adipose tissue hypertrophy, and lipid metabolism in an animal model of diet-induced obesity. To this end, mouse 3T3-F442A preadipocytes were treated with Cr tepals extract and the expression of adipocyte differentiation genes was determined. Caloric intake, body mass, triglycerides, systemic insulin sensitivity, histology, insulin signaling and lipid metabolism in VAT and SAT were analyzed in mice fed a 60% fat diet for 14 weeks and treated orally with Cr tepals extract during the last 5 weeks of the diet. We demonstrated for the first time that Cr tepals extract inhibits adipocyte differentiation in vitro. The animal model confirmed that oral treatment with Cr tepals extract results in weight loss, improved systemic insulin sensitivity, lower triglycerides, and improved lipid peroxidation. The suppressive effect of Cr tepals extract on adipocyte hypertrophy and inflammation was observed only in SAT, which, together with preserved SAT insulin signaling, most likely contributed to improved systemic insulin sensitivity. Our results suggest the functionality of SAT as a possible target for the treatment of obesity and its complications.",
publisher = "Hoboken: John Wiley and Sons",
journal = "BioFactors",
title = "Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet",
doi = "10.1002/biof.2043"
}

Bursać, B., Bellachioma, L., Gligorovska, L., Jovanović, M., Teofilović, A., Vratarić, M., Vojnović Milutinović, D., Albacete, A., Martínez-Melgarejo, P. A., Morresi, C., Damiani, E., Bacchetti, T.,& Đorđević, A.. (2024). Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet. in BioFactors
Hoboken: John Wiley and Sons..
https://doi.org/10.1002/biof.2043

Bursać B, Bellachioma L, Gligorovska L, Jovanović M, Teofilović A, Vratarić M, Vojnović Milutinović D, Albacete A, Martínez-Melgarejo PA, Morresi C, Damiani E, Bacchetti T, Đorđević A. Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet. in BioFactors. 2024;.
doi:10.1002/biof.2043 .

Bursać, Biljana, Bellachioma, Luisa, Gligorovska, Ljupka, Jovanović, Mirna, Teofilović, Ana, Vratarić, Miloš, Vojnović Milutinović, Danijela, Albacete, Alfonso, Martínez-Melgarejo, Purificación A, Morresi, Camilla, Damiani, Elisabetta, Bacchetti, Tiziana, Đorđević, Ana, "Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet" in BioFactors (2024),
https://doi.org/10.1002/biof.2043 . .

TY  - CHAP
AU  - Gligorovska, Ljupka
AU  - Đorđević, Ana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6422
AB  - Hronična inflamacija niskog intenziteta ima važnu ulogu u patogenezi metaboličkih poremećaja, kao što su gojaznost i dislipidemija, koji su često izazvani ishranom obogaćenom fruktozom i predstavljaju faktore rizika za razvoj steatoze jetre i dijabetesa tipa 2. Faktor migracije makrofaga (MIF) je plejotropni citokin koji pored uloge u regulaciji imunskog odgovora može da reguliše metaboličke procese i oslobađanje insulina iz pankreasa, međutim njegova uloga u metaboličkoj inflamaciji nije još uvek dovoljno razjašnjena. Dodatno, pokazano je da se miševi sa deletiranim genom Mif odlikuju izmenjenom osetljivošću na insulin i glukozu. Stoga, fokus ovog rada je bio usmeren ka boljem razumevanju molekularnih mehanizama metaboličkih efekata MIF-a, kao i ka rasvetljavanju kontroverzne uloge ovog citokina u razvoju poremećaja lipidnog metabolizma u jetri i visceralnom masnom tkivu miševa na režimu ishrane obogaćene fruktozom.
AB  - Chronic low-grade inflammation plays an important role in the development of metabolic disorders such as obesity and dyslipidemia, which are often induced by a fructose-enriched diet and are risk factors for the development of hepatic steatosis and type 2 diabetes. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that, in addition to its role in regulating the immune response, can regulate metabolic processes and the release of insulin from the pancreas; however its role in metabolic inflammation is not well understood. In addition, mice with a deleted Mif gene were found to have altered sensitivity to insulin and glucose. Therefore, the focus of this work was to better understand the molecular mechanisms of the metabolic effects of MIF and to elucidate the controversial role of this cytokine in the development ofdyslipidemia in the liver and visceral adipose tissue of mice on fructose-enriched diet.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
T2  - Trends in molecular biology
T1  - Uticaj delecije gena Mif na razvoj gojaznosti i steatoze jetre kod miševa na režimu ishrane obogaćene fruktozom
T1  - The effects of deletion of the Mif gene on the development of obesity and hepatic steatosis on mice on fructose enriched diet
IS  - 3
SP  - 151
EP  - 166
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6422
ER  - 

@inbook{
author = "Gligorovska, Ljupka and Đorđević, Ana",
year = "2023",
abstract = "Hronična inflamacija niskog intenziteta ima važnu ulogu u patogenezi metaboličkih poremećaja, kao što su gojaznost i dislipidemija, koji su često izazvani ishranom obogaćenom fruktozom i predstavljaju faktore rizika za razvoj steatoze jetre i dijabetesa tipa 2. Faktor migracije makrofaga (MIF) je plejotropni citokin koji pored uloge u regulaciji imunskog odgovora može da reguliše metaboličke procese i oslobađanje insulina iz pankreasa, međutim njegova uloga u metaboličkoj inflamaciji nije još uvek dovoljno razjašnjena. Dodatno, pokazano je da se miševi sa deletiranim genom Mif odlikuju izmenjenom osetljivošću na insulin i glukozu. Stoga, fokus ovog rada je bio usmeren ka boljem razumevanju molekularnih mehanizama metaboličkih efekata MIF-a, kao i ka rasvetljavanju kontroverzne uloge ovog citokina u razvoju poremećaja lipidnog metabolizma u jetri i visceralnom masnom tkivu miševa na režimu ishrane obogaćene fruktozom., Chronic low-grade inflammation plays an important role in the development of metabolic disorders such as obesity and dyslipidemia, which are often induced by a fructose-enriched diet and are risk factors for the development of hepatic steatosis and type 2 diabetes. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that, in addition to its role in regulating the immune response, can regulate metabolic processes and the release of insulin from the pancreas; however its role in metabolic inflammation is not well understood. In addition, mice with a deleted Mif gene were found to have altered sensitivity to insulin and glucose. Therefore, the focus of this work was to better understand the molecular mechanisms of the metabolic effects of MIF and to elucidate the controversial role of this cytokine in the development ofdyslipidemia in the liver and visceral adipose tissue of mice on fructose-enriched diet.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Trends in molecular biology",
booktitle = "Uticaj delecije gena Mif na razvoj gojaznosti i steatoze jetre kod miševa na režimu ishrane obogaćene fruktozom, The effects of deletion of the Mif gene on the development of obesity and hepatic steatosis on mice on fructose enriched diet",
number = "3",
pages = "151-166",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6422"
}

Gligorovska, L.,& Đorđević, A.. (2023). Uticaj delecije gena Mif na razvoj gojaznosti i steatoze jetre kod miševa na režimu ishrane obogaćene fruktozom. in Trends in molecular biology
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade.(3), 151-166.
https://hdl.handle.net/21.15107/rcub_ibiss_6422

Gligorovska L, Đorđević A. Uticaj delecije gena Mif na razvoj gojaznosti i steatoze jetre kod miševa na režimu ishrane obogaćene fruktozom. in Trends in molecular biology. 2023;(3):151-166.
https://hdl.handle.net/21.15107/rcub_ibiss_6422 .

Gligorovska, Ljupka, Đorđević, Ana, "Uticaj delecije gena Mif na razvoj gojaznosti i steatoze jetre kod miševa na režimu ishrane obogaćene fruktozom" in Trends in molecular biology, no. 3 (2023):151-166,
https://hdl.handle.net/21.15107/rcub_ibiss_6422 .

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  - THES
AU  - Gligorovska, Ljupka
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5111
AB  - Faktor inhibicije migracije makrofaga (MIF) jedan je od glavnih pro-inflamatornih citokina sa ulogom u metaboličkoj inflamaciji. Metabolička inflamacija niskog intenziteta u visceralnom masnom tkivu i jetri povezana je sa gojaznošću i dislipidemijom - metaboličkim poremećajima koji su često izazvani ishranom obogaćenom fruktozom i predstavljaju faktore rizika za razvoj dijabetesa tipa 2. Cilj ove doktorske disertacije bio je da se utvrdi da li MIF ostvaruje svoj uticaj na lipidni metabolizam u masnom tkivu i jetri posredstvom glukokortikoidnih hormona (GH), važnih regulatora energetskog metabolizma. U tom cilju bili su ispitani najvažniji parametri lipidnog metabolizma i inflamacije, signalni put GH-a, kao i enzimi i transkripcioni regulatori uključeni u lipidni metabolizam, direktno ili indirektno regulisani glukokortikoidnim receptorom, kod miševa „divljeg tipa“ i miševa sa deletiranim genom za MIF (MIF-/-) u normalnim uslovima i pod uslovima energetskog opterećenja izazvanog fruktozom. Rezultati su pokazali da nedostatak gena Mif dovodi do hiperleptinemije, hiperglikemije, hiperinsulinemije i sistemske insulinske rezistencije nezavisno od režima ishrane. Iako nije bilo promena u nivou triglicerida i slobodnih masnih kiselina u krvi, ishrana bogata fruktozom dovela je do pojave visceralne gojaznosti, steatoze jetre, ali i aktivacije signalnog puta GH-a u masnom tkivu i jetri MIF-/- miševa. Inflamacija u masnom tkivu nije zabeležena, dok je u jetri svih MIF-/- miševa primećeno povećanje ekspresije pro-inflamatornih citokina, kao i nekrotične i regenerativne promene. Na osnovu dobijenih rezultata zaključeno je da ishrana obogaćena fruktozom izaziva poremećaj metabolizma glukoze i lipida kod MIF-/- miševa usled pojačane signalizacije GH-a u uslovima insulinske rezistencije.
AB  - Macrophage migration inhibitory factor (MIF) is one of the main pro-inflammatory cytokines with a role in metabolic inflammation. Low-grade inflammation in the visceral adipose tissue and liver is associated with obesity and dyslipidemia - metabolic disorders that are often caused by a fructose-enriched diet and are risk factors for the development of type 2 diabetes. The aim of this doctoral dissertation was to determine whether MIF exerts its influence on lipid metabolism in the adipose tissue and liver through glucocorticoid hormones (GC), important regulators of energy metabolism. To this end, the most important parameters of lipid metabolism and inflammation, the GC signaling pathway, as well as enzymes and transcriptional regulators involved in lipid metabolism, directly or indirectly regulated by the glucocorticoid receptor, were examined in wild type mice and mice with deleted Mif gene (MIF-/-) under normal conditions and under fructose-induced energy overconsumption. The results showed that Mif deficiency leads to hyperleptinemia, hyperglycemia, hyperinsulinemia, and systemic insulin resistance independently of diet. Although there were no changes in blood triglycerides and free fatty acids levels, a fructose-enriched diet led to visceral obesity, liver steatosis, and activation of the GC signaling pathway in adipose tissue and the liver of MIF-/- mice. Inflammation was not found in adipose tissue, while an increase in the expression of pro-inflammatory cytokines, as well as necrotic and regenerative changes, were observed in the liver of all MIF-/- mice. Based on the obtained results, it was concluded that fructose-enriched diet causes disturbances in glucose and lipid metabolism in MIF-/- mice due to enhanced GC signaling in conditions of insulin resistance.
PB  - Belgrade: Faculty of Biology, University of Belgrade
T2  - Faculty of Biology, University of Belgrade
T1  - Metabolizam lipida i signalni put glukokortikoida u visceralnom masnom tkivu i jetri Mif -/- miševa na režimu ishrane obogaćene fruktozom
T1  - The lipid metabolism and glucocorticoid signaling in visceral adipose tissue and liver of Mif -/- mice on fructose enriched diet
EP  - 103
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5111
ER  - 

@phdthesis{
author = "Gligorovska, Ljupka",
year = "2022",
abstract = "Faktor inhibicije migracije makrofaga (MIF) jedan je od glavnih pro-inflamatornih citokina sa ulogom u metaboličkoj inflamaciji. Metabolička inflamacija niskog intenziteta u visceralnom masnom tkivu i jetri povezana je sa gojaznošću i dislipidemijom - metaboličkim poremećajima koji su često izazvani ishranom obogaćenom fruktozom i predstavljaju faktore rizika za razvoj dijabetesa tipa 2. Cilj ove doktorske disertacije bio je da se utvrdi da li MIF ostvaruje svoj uticaj na lipidni metabolizam u masnom tkivu i jetri posredstvom glukokortikoidnih hormona (GH), važnih regulatora energetskog metabolizma. U tom cilju bili su ispitani najvažniji parametri lipidnog metabolizma i inflamacije, signalni put GH-a, kao i enzimi i transkripcioni regulatori uključeni u lipidni metabolizam, direktno ili indirektno regulisani glukokortikoidnim receptorom, kod miševa „divljeg tipa“ i miševa sa deletiranim genom za MIF (MIF-/-) u normalnim uslovima i pod uslovima energetskog opterećenja izazvanog fruktozom. Rezultati su pokazali da nedostatak gena Mif dovodi do hiperleptinemije, hiperglikemije, hiperinsulinemije i sistemske insulinske rezistencije nezavisno od režima ishrane. Iako nije bilo promena u nivou triglicerida i slobodnih masnih kiselina u krvi, ishrana bogata fruktozom dovela je do pojave visceralne gojaznosti, steatoze jetre, ali i aktivacije signalnog puta GH-a u masnom tkivu i jetri MIF-/- miševa. Inflamacija u masnom tkivu nije zabeležena, dok je u jetri svih MIF-/- miševa primećeno povećanje ekspresije pro-inflamatornih citokina, kao i nekrotične i regenerativne promene. Na osnovu dobijenih rezultata zaključeno je da ishrana obogaćena fruktozom izaziva poremećaj metabolizma glukoze i lipida kod MIF-/- miševa usled pojačane signalizacije GH-a u uslovima insulinske rezistencije., Macrophage migration inhibitory factor (MIF) is one of the main pro-inflammatory cytokines with a role in metabolic inflammation. Low-grade inflammation in the visceral adipose tissue and liver is associated with obesity and dyslipidemia - metabolic disorders that are often caused by a fructose-enriched diet and are risk factors for the development of type 2 diabetes. The aim of this doctoral dissertation was to determine whether MIF exerts its influence on lipid metabolism in the adipose tissue and liver through glucocorticoid hormones (GC), important regulators of energy metabolism. To this end, the most important parameters of lipid metabolism and inflammation, the GC signaling pathway, as well as enzymes and transcriptional regulators involved in lipid metabolism, directly or indirectly regulated by the glucocorticoid receptor, were examined in wild type mice and mice with deleted Mif gene (MIF-/-) under normal conditions and under fructose-induced energy overconsumption. The results showed that Mif deficiency leads to hyperleptinemia, hyperglycemia, hyperinsulinemia, and systemic insulin resistance independently of diet. Although there were no changes in blood triglycerides and free fatty acids levels, a fructose-enriched diet led to visceral obesity, liver steatosis, and activation of the GC signaling pathway in adipose tissue and the liver of MIF-/- mice. Inflammation was not found in adipose tissue, while an increase in the expression of pro-inflammatory cytokines, as well as necrotic and regenerative changes, were observed in the liver of all MIF-/- mice. Based on the obtained results, it was concluded that fructose-enriched diet causes disturbances in glucose and lipid metabolism in MIF-/- mice due to enhanced GC signaling in conditions of insulin resistance.",
publisher = "Belgrade: Faculty of Biology, University of Belgrade",
journal = "Faculty of Biology, University of Belgrade",
title = "Metabolizam lipida i signalni put glukokortikoida u visceralnom masnom tkivu i jetri Mif -/- miševa na režimu ishrane obogaćene fruktozom, The lipid metabolism and glucocorticoid signaling in visceral adipose tissue and liver of Mif -/- mice on fructose enriched diet",
pages = "103",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5111"
}

Gligorovska, L.. (2022). Metabolizam lipida i signalni put glukokortikoida u visceralnom masnom tkivu i jetri Mif -/- miševa na režimu ishrane obogaćene fruktozom. in Faculty of Biology, University of Belgrade
Belgrade: Faculty of Biology, University of Belgrade..
https://hdl.handle.net/21.15107/rcub_ibiss_5111

Gligorovska L. Metabolizam lipida i signalni put glukokortikoida u visceralnom masnom tkivu i jetri Mif -/- miševa na režimu ishrane obogaćene fruktozom. in Faculty of Biology, University of Belgrade. 2022;:null-103.
https://hdl.handle.net/21.15107/rcub_ibiss_5111 .

Gligorovska, Ljupka, "Metabolizam lipida i signalni put glukokortikoida u visceralnom masnom tkivu i jetri Mif -/- miševa na režimu ishrane obogaćene fruktozom" in Faculty of Biology, University of Belgrade (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5111 .

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 . .

TY  - JOUR
AU  - Gligorovska, Ljupka
AU  - Teofilović, Ana
AU  - Vojnović-Milutinović, Danijela
AU  - Miladinović, Nenad
AU  - Kovačević, Sanja
AU  - Veličković, Nataša
AU  - Đorđević, Ana
PY  - 2021
UR  - https://onlinelibrary.wiley.com/doi/10.1002/biof.1711
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4148
AB  - Dietary fructose can disturb hepatic lipid metabolism in a way that leads to lipid accumulation and steatosis, which is often accompanied with low-grade inflammation. The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with important role not only in the regulation of inflammation, but also in the modulation of energy metabolism in the liver. Thus, the aim of this study was to investigate the role of Mif deficiency in fructose-induced disturbances of hepatic lipid metabolism and ectopic lipid accumulation. Wild type (WT) and Mif deficient (MIF−/−) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on hepatic lipid metabolism (both lipogenesis and β-oxidation) and histology, inflammatory status and glucocorticoid receptor (GR) signaling. The results showed fructose-induced elevation of lipogenic genes (fatty acid synthase (Fas) and stearoyl-CoA desaturase-1 (Scd1) and transcriptional lipogenic regulators (liver X receptor (LXR), sterol regulatory element binding protein 1c (SREBP1c), and carbohydrate response element-binding protein (ChREBP)). However, microvesicular fatty changes, accompanied with enhanced inflammation, were observable only in fructose-fed Mif deficient animals, and were most likely result of GR activation and facilitated uptake and decreased β-oxidation of FFA, as evidenced by elevated protein level of fatty acid translocase (FAT/CD36) and decreased carnitine palmitoyl transferase 1 (CPT1) level. In conclusion, the results show that Mif deficiency aggravates the effects of energy-rich fructose diet on hepatic lipid accumulation, most likely through enhanced inflammation and activation of GR signaling pathway.
PB  - Blackwell Publishing Inc.
T2  - BioFactors
T1  - Macrophage migration inhibitory factor deficiency aggravates effects of fructose‐enriched diet on lipid metabolism in the mouse liver
DO  - 10.1002/biof.1711
SP  - biof.1711
ER  - 

@article{
author = "Gligorovska, Ljupka and Teofilović, Ana and Vojnović-Milutinović, Danijela and Miladinović, Nenad and Kovačević, Sanja and Veličković, Nataša and Đorđević, Ana",
year = "2021",
abstract = "Dietary fructose can disturb hepatic lipid metabolism in a way that leads to lipid accumulation and steatosis, which is often accompanied with low-grade inflammation. The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with important role not only in the regulation of inflammation, but also in the modulation of energy metabolism in the liver. Thus, the aim of this study was to investigate the role of Mif deficiency in fructose-induced disturbances of hepatic lipid metabolism and ectopic lipid accumulation. Wild type (WT) and Mif deficient (MIF−/−) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on hepatic lipid metabolism (both lipogenesis and β-oxidation) and histology, inflammatory status and glucocorticoid receptor (GR) signaling. The results showed fructose-induced elevation of lipogenic genes (fatty acid synthase (Fas) and stearoyl-CoA desaturase-1 (Scd1) and transcriptional lipogenic regulators (liver X receptor (LXR), sterol regulatory element binding protein 1c (SREBP1c), and carbohydrate response element-binding protein (ChREBP)). However, microvesicular fatty changes, accompanied with enhanced inflammation, were observable only in fructose-fed Mif deficient animals, and were most likely result of GR activation and facilitated uptake and decreased β-oxidation of FFA, as evidenced by elevated protein level of fatty acid translocase (FAT/CD36) and decreased carnitine palmitoyl transferase 1 (CPT1) level. In conclusion, the results show that Mif deficiency aggravates the effects of energy-rich fructose diet on hepatic lipid accumulation, most likely through enhanced inflammation and activation of GR signaling pathway.",
publisher = "Blackwell Publishing Inc.",
journal = "BioFactors",
title = "Macrophage migration inhibitory factor deficiency aggravates effects of fructose‐enriched diet on lipid metabolism in the mouse liver",
doi = "10.1002/biof.1711",
pages = "biof.1711"
}

Gligorovska, L., Teofilović, A., Vojnović-Milutinović, D., Miladinović, N., Kovačević, S., Veličković, N.,& Đorđević, A.. (2021). Macrophage migration inhibitory factor deficiency aggravates effects of fructose‐enriched diet on lipid metabolism in the mouse liver. in BioFactors
Blackwell Publishing Inc.., biof.1711.
https://doi.org/10.1002/biof.1711

Gligorovska L, Teofilović A, Vojnović-Milutinović D, Miladinović N, Kovačević S, Veličković N, Đorđević A. Macrophage migration inhibitory factor deficiency aggravates effects of fructose‐enriched diet on lipid metabolism in the mouse liver. in BioFactors. 2021;:biof.1711.
doi:10.1002/biof.1711 .

Gligorovska, Ljupka, Teofilović, Ana, Vojnović-Milutinović, Danijela, Miladinović, Nenad, Kovačević, Sanja, Veličković, Nataša, Đorđević, Ana, "Macrophage migration inhibitory factor deficiency aggravates effects of fructose‐enriched diet on lipid metabolism in the mouse liver" in BioFactors (2021):biof.1711,
https://doi.org/10.1002/biof.1711 . .

TY  - JOUR
AU  - Vratarić, Miloš
AU  - Šenk, Vladimir
AU  - Bursać, Biljana
AU  - Gligorovska, Ljupka
AU  - Ignjatović, Đurđica
AU  - Kovačević, Sanja
AU  - Veličković, Nataša
AU  - Đorđević, Ana
PY  - 2021
UR  - https://onlinelibrary.wiley.com/doi/10.1002/biof.1802
UR  - http://www.ncbi.nlm.nih.gov/pubmed/34767656
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4687
AB  - Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that represents a link between diet-induced inflammation and insulin resistance. Our aim was to examine whether fructose diet affects inflammation and insulin signaling in the prefrontal cortex (PFC) of Mif knockout mice (MIF-KO), and their possible link to neural plasticity and behavior. We analyzed nuclear factor κB (NF-κB) and glucocorticoid signaling, expression of F4/80, IL-1β, TNF-α, TLR-4, MyD88, arginase 1 (Arg-1), mannose receptor (Mrc-1), and leukemia inhibitory factor (Lif) to assess inflammation in the PFC of C57/BL6J and MIF-KO mice consuming 20% fructose solution for 9 weeks. Insulin receptor (IR), IRS-1 serine phosphorylations (307 and 1101) and activity of PKCα, Akt, GSK-3β and AMPKα were used to analyze insulin signaling. Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) mRNA levels, together with synapthophysin and PSD-95 protein level and calcium calmodulin-dependent kinase 2 (CaMKII) activity, were used as plasticity markers. Behavior was examined in elevated plus maze, light dark box and novel object recognition test. The results showed concomitant increase of Tnf-α, Tlr-4, MyD88 and M2 microglia markers (Arg-1, Mrc-1, Lif) in the PFC of MIF-KO, paralleled with unchanged glucocorticoid and insulin signaling. Increase of BDNF and IGF-1 was paralleled with increased CaMKII activity, decreased PSD-95 protein level, anxiogenic behavior, and impaired memory in MIF-KO mice. Fructose feeding restored these parameters in the PFC to the control level and mitigated behavioral changes, suggesting that ameliorating effects of fructose on neuroinflammation and behavior depend on the presence of MIF.
T2  - BioFactors (Oxford, England)
T1  - Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice.
DO  - 10.1002/biof.1802
ER  - 

@article{
author = "Vratarić, Miloš and Šenk, Vladimir and Bursać, Biljana and Gligorovska, Ljupka and Ignjatović, Đurđica and Kovačević, Sanja and Veličković, Nataša and Đorđević, Ana",
year = "2021",
abstract = "Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that represents a link between diet-induced inflammation and insulin resistance. Our aim was to examine whether fructose diet affects inflammation and insulin signaling in the prefrontal cortex (PFC) of Mif knockout mice (MIF-KO), and their possible link to neural plasticity and behavior. We analyzed nuclear factor κB (NF-κB) and glucocorticoid signaling, expression of F4/80, IL-1β, TNF-α, TLR-4, MyD88, arginase 1 (Arg-1), mannose receptor (Mrc-1), and leukemia inhibitory factor (Lif) to assess inflammation in the PFC of C57/BL6J and MIF-KO mice consuming 20% fructose solution for 9 weeks. Insulin receptor (IR), IRS-1 serine phosphorylations (307 and 1101) and activity of PKCα, Akt, GSK-3β and AMPKα were used to analyze insulin signaling. Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) mRNA levels, together with synapthophysin and PSD-95 protein level and calcium calmodulin-dependent kinase 2 (CaMKII) activity, were used as plasticity markers. Behavior was examined in elevated plus maze, light dark box and novel object recognition test. The results showed concomitant increase of Tnf-α, Tlr-4, MyD88 and M2 microglia markers (Arg-1, Mrc-1, Lif) in the PFC of MIF-KO, paralleled with unchanged glucocorticoid and insulin signaling. Increase of BDNF and IGF-1 was paralleled with increased CaMKII activity, decreased PSD-95 protein level, anxiogenic behavior, and impaired memory in MIF-KO mice. Fructose feeding restored these parameters in the PFC to the control level and mitigated behavioral changes, suggesting that ameliorating effects of fructose on neuroinflammation and behavior depend on the presence of MIF.",
journal = "BioFactors (Oxford, England)",
title = "Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice.",
doi = "10.1002/biof.1802"
}

Vratarić, M., Šenk, V., Bursać, B., Gligorovska, L., Ignjatović, Đ., Kovačević, S., Veličković, N.,& Đorđević, A.. (2021). Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice.. in BioFactors (Oxford, England).
https://doi.org/10.1002/biof.1802

Vratarić M, Šenk V, Bursać B, Gligorovska L, Ignjatović Đ, Kovačević S, Veličković N, Đorđević A. Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice.. in BioFactors (Oxford, England). 2021;.
doi:10.1002/biof.1802 .

Vratarić, Miloš, Šenk, Vladimir, Bursać, Biljana, Gligorovska, Ljupka, Ignjatović, Đurđica, Kovačević, Sanja, Veličković, Nataša, Đorđević, Ana, "Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice." in BioFactors (Oxford, England) (2021),
https://doi.org/10.1002/biof.1802 . .

TY  - JOUR
AU  - Kovačević, Sanja
AU  - Brkljačić, Jelena
AU  - Vojnović-Milutinović, Danijela
AU  - Gligorovska, Ljupka
AU  - Bursać, Biljana
AU  - Elaković, Ivana
AU  - Đorđević, Ana
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4705
AB  - Introduction: Obesity and related metabolic disturbances are frequently related to
modern lifestyle and are characterized by excessive fructose intake. Visceral adipose
tissue (VAT) inflammation has a central role in the development of insulin resistance, type
2 diabetes (T2D), and metabolic syndrome. Since sex-related differences in susceptibility
and progression of metabolic disorders are not yet fully understood, our aim was to
examine inflammation and insulin signaling in VAT of fructose-fed female and male
adult rats.
Methods: We analyzed effects of 9-week 10% fructose-enriched diet on energy intake,
VATmass and histology, and systemic insulin sensitivity. VAT insulin signaling andmarkers
of VAT inflammation, and antioxidative defense status were also evaluated.
Results: The fructose diet had no effect on VAT mass and systemic insulin signaling
in the female and male rats, while it raised plasma uric acid, increased PPARg level in
the VAT, and initiated the development of a distinctive population of small adipocytes
in the females. Also, adipose tissue insulin resistance, evidenced by increased PTP1B
and insulin receptor substrate 1 (IRS1) inhibitory phosphorylation and decreased Akt
activity, was detected. In addition, fructose stimulated the nuclear accumulation of NFkB,
increased expression of proinflammatory cytokines (IL-1b, IL-6, and TNFα), and protein
level of macrophage marker F4/80, superoxide dismutase 1, and glutathione reductase.
In contrast to the females, the fructose diet had no effect on plasma uric acid and
VAT inflammation in the male rats, but less prominent alterations in VAT insulin signaling
were observed.
Conclusion: Even though dietary fructose did not elicit changes in energy intake and
led to obesity in the females, it initiated the proliferation of small-sized adipocytes capable
of storing fats further. In contrast to the males, this state of VAT was accompanied
with enhanced inflammation, which most likely contributed to the development of insulin
resistance. The observed distinction could possibly originate from sex-related differences
in uric acid metabolism. Our results suggest that VAT inflammation could precede obesity and start even before the measurable increase in VAT mass, making it a silent risk factor
for the development of T2D. Our results emphasize that adipose tissue dysfunction,
rather than its simple enlargement, could significantly contribute to the onset and
development of obesity and related metabolic disorders.
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Nutrition
T1  - Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats
VL  - 8
DO  - 10.3389/fnut.2021.749328
SP  - 749328
ER  - 

@article{
author = "Kovačević, Sanja and Brkljačić, Jelena and Vojnović-Milutinović, Danijela and Gligorovska, Ljupka and Bursać, Biljana and Elaković, Ivana and Đorđević, Ana",
year = "2021",
abstract = "Introduction: Obesity and related metabolic disturbances are frequently related to
modern lifestyle and are characterized by excessive fructose intake. Visceral adipose
tissue (VAT) inflammation has a central role in the development of insulin resistance, type
2 diabetes (T2D), and metabolic syndrome. Since sex-related differences in susceptibility
and progression of metabolic disorders are not yet fully understood, our aim was to
examine inflammation and insulin signaling in VAT of fructose-fed female and male
adult rats.
Methods: We analyzed effects of 9-week 10% fructose-enriched diet on energy intake,
VATmass and histology, and systemic insulin sensitivity. VAT insulin signaling andmarkers
of VAT inflammation, and antioxidative defense status were also evaluated.
Results: The fructose diet had no effect on VAT mass and systemic insulin signaling
in the female and male rats, while it raised plasma uric acid, increased PPARg level in
the VAT, and initiated the development of a distinctive population of small adipocytes
in the females. Also, adipose tissue insulin resistance, evidenced by increased PTP1B
and insulin receptor substrate 1 (IRS1) inhibitory phosphorylation and decreased Akt
activity, was detected. In addition, fructose stimulated the nuclear accumulation of NFkB,
increased expression of proinflammatory cytokines (IL-1b, IL-6, and TNFα), and protein
level of macrophage marker F4/80, superoxide dismutase 1, and glutathione reductase.
In contrast to the females, the fructose diet had no effect on plasma uric acid and
VAT inflammation in the male rats, but less prominent alterations in VAT insulin signaling
were observed.
Conclusion: Even though dietary fructose did not elicit changes in energy intake and
led to obesity in the females, it initiated the proliferation of small-sized adipocytes capable
of storing fats further. In contrast to the males, this state of VAT was accompanied
with enhanced inflammation, which most likely contributed to the development of insulin
resistance. The observed distinction could possibly originate from sex-related differences
in uric acid metabolism. Our results suggest that VAT inflammation could precede obesity and start even before the measurable increase in VAT mass, making it a silent risk factor
for the development of T2D. Our results emphasize that adipose tissue dysfunction,
rather than its simple enlargement, could significantly contribute to the onset and
development of obesity and related metabolic disorders.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Nutrition",
title = "Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats",
volume = "8",
doi = "10.3389/fnut.2021.749328",
pages = "749328"
}

Kovačević, S., Brkljačić, J., Vojnović-Milutinović, D., Gligorovska, L., Bursać, B., Elaković, I.,& Đorđević, A.. (2021). Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats. in Frontiers in Nutrition
Lausanne: Frontiers Media SA., 8, 749328.
https://doi.org/10.3389/fnut.2021.749328

Kovačević S, Brkljačić J, Vojnović-Milutinović D, Gligorovska L, Bursać B, Elaković I, Đorđević A. Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats. in Frontiers in Nutrition. 2021;8:749328.
doi:10.3389/fnut.2021.749328 .

Kovačević, Sanja, Brkljačić, Jelena, Vojnović-Milutinović, Danijela, Gligorovska, Ljupka, Bursać, Biljana, Elaković, Ivana, Đorđević, Ana, "Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats" in Frontiers in Nutrition, 8 (2021):749328,
https://doi.org/10.3389/fnut.2021.749328 . .

TY  - JOUR
AU  - Vratarić, Miloš
AU  - Šenk, Vladimir
AU  - Bursać, Biljana
AU  - Gligorovska, Ljupka
AU  - Ignjatović, Đurđica
AU  - Kovačević, Sanja
AU  - Veličković, Nataša
AU  - Đorđević, Ana
PY  - 2021
UR  - https://onlinelibrary.wiley.com/doi/10.1002/biof.1802
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4773
AB  - Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that represents a link between diet-induced inflammation and insulin resistance. Our aim was to examine whether fructose diet affects inflammation and insulin signaling in the prefrontal cortex (PFC) of Mif knockout mice (MIF-KO), and their possible link to neural plasticity and behavior. We analyzed nuclear factor κB (NF-κB) and glucocorticoid signaling, expression of F4/80, IL-1β, TNF-α, TLR-4, MyD88, arginase 1 (Arg-1), mannose receptor (Mrc-1), and leukemia inhibitory factor (Lif) to assess inflammation in the PFC of C57/BL6J and MIF-KO mice consuming 20% fructose solution for 9 weeks. Insulin receptor (IR), IRS-1 serine phosphorylations (307 and 1101) and activity of PKCα, Akt, GSK-3β and AMPKα were used to analyze insulin signaling. Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) mRNA levels, together with synapthophysin and PSD-95 protein level and calcium calmodulin-dependent kinase 2 (CaMKII) activity, were used as plasticity markers. Behavior was examined in elevated plus maze, light dark box and novel object recognition test. The results showed concomitant increase of Tnf-α, Tlr-4, MyD88 and M2 microglia markers (Arg-1, Mrc-1, Lif) in the PFC of MIF-KO, paralleled with unchanged glucocorticoid and insulin signaling. Increase of BDNF and IGF-1 was paralleled with increased CaMKII activity, decreased PSD-95 protein level, anxiogenic behavior, and impaired memory in MIF-KO mice. Fructose feeding restored these parameters in the PFC to the control level and mitigated behavioral changes, suggesting that ameliorating effects of fructose on neuroinflammation and behavior depend on the presence of MIF.
T2  - BioFactors (Oxford, England)
T1  - Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice.
DO  - 10.1002/biof.1802
ER  - 

@article{
author = "Vratarić, Miloš and Šenk, Vladimir and Bursać, Biljana and Gligorovska, Ljupka and Ignjatović, Đurđica and Kovačević, Sanja and Veličković, Nataša and Đorđević, Ana",
year = "2021",
abstract = "Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that represents a link between diet-induced inflammation and insulin resistance. Our aim was to examine whether fructose diet affects inflammation and insulin signaling in the prefrontal cortex (PFC) of Mif knockout mice (MIF-KO), and their possible link to neural plasticity and behavior. We analyzed nuclear factor κB (NF-κB) and glucocorticoid signaling, expression of F4/80, IL-1β, TNF-α, TLR-4, MyD88, arginase 1 (Arg-1), mannose receptor (Mrc-1), and leukemia inhibitory factor (Lif) to assess inflammation in the PFC of C57/BL6J and MIF-KO mice consuming 20% fructose solution for 9 weeks. Insulin receptor (IR), IRS-1 serine phosphorylations (307 and 1101) and activity of PKCα, Akt, GSK-3β and AMPKα were used to analyze insulin signaling. Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) mRNA levels, together with synapthophysin and PSD-95 protein level and calcium calmodulin-dependent kinase 2 (CaMKII) activity, were used as plasticity markers. Behavior was examined in elevated plus maze, light dark box and novel object recognition test. The results showed concomitant increase of Tnf-α, Tlr-4, MyD88 and M2 microglia markers (Arg-1, Mrc-1, Lif) in the PFC of MIF-KO, paralleled with unchanged glucocorticoid and insulin signaling. Increase of BDNF and IGF-1 was paralleled with increased CaMKII activity, decreased PSD-95 protein level, anxiogenic behavior, and impaired memory in MIF-KO mice. Fructose feeding restored these parameters in the PFC to the control level and mitigated behavioral changes, suggesting that ameliorating effects of fructose on neuroinflammation and behavior depend on the presence of MIF.",
journal = "BioFactors (Oxford, England)",
title = "Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice.",
doi = "10.1002/biof.1802"
}

Vratarić, M., Šenk, V., Bursać, B., Gligorovska, L., Ignjatović, Đ., Kovačević, S., Veličković, N.,& Đorđević, A.. (2021). Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice.. in BioFactors (Oxford, England).
https://doi.org/10.1002/biof.1802

Vratarić M, Šenk V, Bursać B, Gligorovska L, Ignjatović Đ, Kovačević S, Veličković N, Đorđević A. Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice.. in BioFactors (Oxford, England). 2021;.
doi:10.1002/biof.1802 .

Vratarić, Miloš, Šenk, Vladimir, Bursać, Biljana, Gligorovska, Ljupka, Ignjatović, Đurđica, Kovačević, Sanja, Veličković, Nataša, Đorđević, Ana, "Fructose diet ameliorates effects of macrophage migration inhibitory factor deficiency on prefrontal cortex inflammation, neural plasticity, and behavior in male mice." in BioFactors (Oxford, England) (2021),
https://doi.org/10.1002/biof.1802 . .

TY  - JOUR
AU  - Vojnović-Milutinović, Danijela
AU  - Brkljačić, Jelena
AU  - Teofilović, Ana
AU  - Bursać, Biljana
AU  - Radovanović, Marina
AU  - Gligorovska, Ljupka
AU  - Kovačević, Sanja
AU  - Đorđević, Ana
AU  - Preitner, Frederic
AU  - Tappy, Luc
AU  - Matić, Gordana
AU  - Veličković, Nataša
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201901141
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32379936
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3702
AB  - SCOPE Intake of fructose-sweetened beverages and chronic stress (CS) both increase risk of cardiometabolic diseases. The aim is to investigate whether these factors synergistically perturb lipid metabolism in rat liver and kidney. METHODS AND RESULTS Fractional de novo lipogenesis (fDNL), intrahepatic- and intrarenal-triglycerides (IHTG and IRTG), de novo palmitate (DNPalm) content, FA composition, VLDL-TGs kinetics, and key metabolic gene expression at the end of the feeding and non-feeding phases in rats exposed to standard chow diet, chow diet + CS, 20% liquid high-fructose supplementation (HFr), or HFr+CS are measured. HFr induces hypertriglyceridemia, up-regulates fructose-metabolism and gluconeogenic enzymes, increases IHTG and DNPalm content in IHTG and IRTG, and augments fDNL at the end of the feeding phase. These changes are diminished after the non-feeding phase. CS does not exert such effects, but when combined with HFr, it reduces IHTG and visceral adiposity, enhances lipogenic gene expression and fDNL, and increases VLDL-DNPalm secretion. CONCLUSION Liquid high-fructose supplementation increases IHTG and VLDL-TG secretion after the feeding phase, the latter being the result of stimulated hepatic and renal DNL. Chronic stress potentiates the effects of high fructose on fDNL and export of newly synthesized VLDL-TGs, and decreases fructose-induced intrahepatic TG accumulation after the feeding phase.
PB  - John Wiley & Sons, Ltd
T2  - Molecular Nutrition & Food Research
T1  - Chronic Stress Potentiates High Fructose-Induced Lipogenesis in Rat Liver and Kidney.
IS  - 13
VL  - 64
DO  - 10.1002/mnfr.201901141
SP  - e1901141
ER  - 

@article{
author = "Vojnović-Milutinović, Danijela and Brkljačić, Jelena and Teofilović, Ana and Bursać, Biljana and Radovanović, Marina and Gligorovska, Ljupka and Kovačević, Sanja and Đorđević, Ana and Preitner, Frederic and Tappy, Luc and Matić, Gordana and Veličković, Nataša",
year = "2020",
abstract = "SCOPE Intake of fructose-sweetened beverages and chronic stress (CS) both increase risk of cardiometabolic diseases. The aim is to investigate whether these factors synergistically perturb lipid metabolism in rat liver and kidney. METHODS AND RESULTS Fractional de novo lipogenesis (fDNL), intrahepatic- and intrarenal-triglycerides (IHTG and IRTG), de novo palmitate (DNPalm) content, FA composition, VLDL-TGs kinetics, and key metabolic gene expression at the end of the feeding and non-feeding phases in rats exposed to standard chow diet, chow diet + CS, 20% liquid high-fructose supplementation (HFr), or HFr+CS are measured. HFr induces hypertriglyceridemia, up-regulates fructose-metabolism and gluconeogenic enzymes, increases IHTG and DNPalm content in IHTG and IRTG, and augments fDNL at the end of the feeding phase. These changes are diminished after the non-feeding phase. CS does not exert such effects, but when combined with HFr, it reduces IHTG and visceral adiposity, enhances lipogenic gene expression and fDNL, and increases VLDL-DNPalm secretion. CONCLUSION Liquid high-fructose supplementation increases IHTG and VLDL-TG secretion after the feeding phase, the latter being the result of stimulated hepatic and renal DNL. Chronic stress potentiates the effects of high fructose on fDNL and export of newly synthesized VLDL-TGs, and decreases fructose-induced intrahepatic TG accumulation after the feeding phase.",
publisher = "John Wiley & Sons, Ltd",
journal = "Molecular Nutrition & Food Research",
title = "Chronic Stress Potentiates High Fructose-Induced Lipogenesis in Rat Liver and Kidney.",
number = "13",
volume = "64",
doi = "10.1002/mnfr.201901141",
pages = "e1901141"
}

Vojnović-Milutinović, D., Brkljačić, J., Teofilović, A., Bursać, B., Radovanović, M., Gligorovska, L., Kovačević, S., Đorđević, A., Preitner, F., Tappy, L., Matić, G.,& Veličković, N.. (2020). Chronic Stress Potentiates High Fructose-Induced Lipogenesis in Rat Liver and Kidney.. in Molecular Nutrition & Food Research
John Wiley & Sons, Ltd., 64(13), e1901141.
https://doi.org/10.1002/mnfr.201901141

Vojnović-Milutinović D, Brkljačić J, Teofilović A, Bursać B, Radovanović M, Gligorovska L, Kovačević S, Đorđević A, Preitner F, Tappy L, Matić G, Veličković N. Chronic Stress Potentiates High Fructose-Induced Lipogenesis in Rat Liver and Kidney.. in Molecular Nutrition & Food Research. 2020;64(13):e1901141.
doi:10.1002/mnfr.201901141 .

Vojnović-Milutinović, Danijela, Brkljačić, Jelena, Teofilović, Ana, Bursać, Biljana, Radovanović, Marina, Gligorovska, Ljupka, Kovačević, Sanja, Đorđević, Ana, Preitner, Frederic, Tappy, Luc, Matić, Gordana, Veličković, Nataša, "Chronic Stress Potentiates High Fructose-Induced Lipogenesis in Rat Liver and Kidney." in Molecular Nutrition & Food Research, 64, no. 13 (2020):e1901141,
https://doi.org/10.1002/mnfr.201901141 . .

TY  - CONF
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Brkljačić, Jelena
AU  - Teofilović, Ana
AU  - Bursać, Biljana
AU  - Radovanović, Marina
AU  - Gligorovska, Ljupka
AU  - Kovačević, Sanja
AU  - Đorđević, Ana
AU  - Preitner, Frédéric
AU  - Tappy, Luc
AU  - Matić, Gordana
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4117
AB  - Overconsumption of fructoseenriched beverages and everyday stress are
both involved in the pathogenesis of metabolic disorders through their effects
on hepatic lipid metabolism. The aim of this study was to investigate
whether highfructose diet and chronic stress synergistically perturbs lipid
metabolism in rat liver. Therefore, we analyzed the effects of 9-week
20% liquid fructose diet and 4-week chronic unpredictable stress, separately
and in combination, on dyslipidemia, VLDL-TG kinetics, intrahepatic
triglycerides (IHTG), liver de novo palmitate (DNPalm) content and fatty
acid (FA) composition. In parallel, hepatic fractional de novo lipogenesis
(fDNL) by stable isotope tracer protocol, as well as expression of lipid metabolism
regulators were also analyzed. Results showed that highfructose
diet led to hypertriglyceridemia, increased plasma VLDL-TGs and free FA
(FFA), and increased visceral adiposity. Fructose diet also augmented the level of palmitate, palmitoleate and oleate in the liver, the latter being result
of increased desaturase activity. In addition, newly synthesized palmitate
(DNPalm content) was increased in the liver of fructose-fed animals,
most likely as a result of stimulated fDNL. Chronic stress alone did not
exert such effects, but when combined with fructose, stress decreased FFA
level, ameliorated fructose-induced TG accumulation, and augmented the
release of VLDL-TGs. Stress also enhanced the effects of high-fructose
diet on fDNL, which was accompanied with increased expression of key
regulators of lipid metabolism, that resulting in stimulated export of newly
synthesized palmitate in the form of VLDL-TGs. These results imply that
high-fructose diet affects hepatic lipid metabolism by stimulating fDNL
and increasing de novo synthesized palmitate, which is partially accumulated
in the liver and in part released into circulation in the form of VLDLTGs.
On the other hand, stress in combination with high-fructose diet
potentiated hepatic fDNL, but it decreased temporary TG storage and redirected
newly synthesized palmitate into VLDL-TGs. Thus, the combination
of high-fructose diet and chronic stress, as hallmarks of modern lifestyle,
exerts more detrimental influence on lipid homeostasis than the individual
factors, judged by stimulated fDNL and increased export of VLDL-TGs to
non-hepatic tissues.
PB  - European Society of Endocrinology
C3  - 22nd European Congress of Endocrinology; 2020 Sep 5-9
T1  - Fructose-induced alterations of hepatic lipid metabolism are modulated by chronic stress in male rats
DO  - 10.1530/endoabs.70.AEP435
SP  - AEP435
ER  - 

@conference{
author = "Veličković, Nataša and Vojnović-Milutinović, Danijela and Brkljačić, Jelena and Teofilović, Ana and Bursać, Biljana and Radovanović, Marina and Gligorovska, Ljupka and Kovačević, Sanja and Đorđević, Ana and Preitner, Frédéric and Tappy, Luc and Matić, Gordana",
year = "2020",
abstract = "Overconsumption of fructoseenriched beverages and everyday stress are
both involved in the pathogenesis of metabolic disorders through their effects
on hepatic lipid metabolism. The aim of this study was to investigate
whether highfructose diet and chronic stress synergistically perturbs lipid
metabolism in rat liver. Therefore, we analyzed the effects of 9-week
20% liquid fructose diet and 4-week chronic unpredictable stress, separately
and in combination, on dyslipidemia, VLDL-TG kinetics, intrahepatic
triglycerides (IHTG), liver de novo palmitate (DNPalm) content and fatty
acid (FA) composition. In parallel, hepatic fractional de novo lipogenesis
(fDNL) by stable isotope tracer protocol, as well as expression of lipid metabolism
regulators were also analyzed. Results showed that highfructose
diet led to hypertriglyceridemia, increased plasma VLDL-TGs and free FA
(FFA), and increased visceral adiposity. Fructose diet also augmented the level of palmitate, palmitoleate and oleate in the liver, the latter being result
of increased desaturase activity. In addition, newly synthesized palmitate
(DNPalm content) was increased in the liver of fructose-fed animals,
most likely as a result of stimulated fDNL. Chronic stress alone did not
exert such effects, but when combined with fructose, stress decreased FFA
level, ameliorated fructose-induced TG accumulation, and augmented the
release of VLDL-TGs. Stress also enhanced the effects of high-fructose
diet on fDNL, which was accompanied with increased expression of key
regulators of lipid metabolism, that resulting in stimulated export of newly
synthesized palmitate in the form of VLDL-TGs. These results imply that
high-fructose diet affects hepatic lipid metabolism by stimulating fDNL
and increasing de novo synthesized palmitate, which is partially accumulated
in the liver and in part released into circulation in the form of VLDLTGs.
On the other hand, stress in combination with high-fructose diet
potentiated hepatic fDNL, but it decreased temporary TG storage and redirected
newly synthesized palmitate into VLDL-TGs. Thus, the combination
of high-fructose diet and chronic stress, as hallmarks of modern lifestyle,
exerts more detrimental influence on lipid homeostasis than the individual
factors, judged by stimulated fDNL and increased export of VLDL-TGs to
non-hepatic tissues.",
publisher = "European Society of Endocrinology",
journal = "22nd European Congress of Endocrinology; 2020 Sep 5-9",
title = "Fructose-induced alterations of hepatic lipid metabolism are modulated by chronic stress in male rats",
doi = "10.1530/endoabs.70.AEP435",
pages = "AEP435"
}

Veličković, N., Vojnović-Milutinović, D., Brkljačić, J., Teofilović, A., Bursać, B., Radovanović, M., Gligorovska, L., Kovačević, S., Đorđević, A., Preitner, F., Tappy, L.,& Matić, G.. (2020). Fructose-induced alterations of hepatic lipid metabolism are modulated by chronic stress in male rats. in 22nd European Congress of Endocrinology; 2020 Sep 5-9
European Society of Endocrinology., AEP435.
https://doi.org/10.1530/endoabs.70.AEP435

Veličković N, Vojnović-Milutinović D, Brkljačić J, Teofilović A, Bursać B, Radovanović M, Gligorovska L, Kovačević S, Đorđević A, Preitner F, Tappy L, Matić G. Fructose-induced alterations of hepatic lipid metabolism are modulated by chronic stress in male rats. in 22nd European Congress of Endocrinology; 2020 Sep 5-9. 2020;:AEP435.
doi:10.1530/endoabs.70.AEP435 .

Veličković, Nataša, Vojnović-Milutinović, Danijela, Brkljačić, Jelena, Teofilović, Ana, Bursać, Biljana, Radovanović, Marina, Gligorovska, Ljupka, Kovačević, Sanja, Đorđević, Ana, Preitner, Frédéric, Tappy, Luc, Matić, Gordana, "Fructose-induced alterations of hepatic lipid metabolism are modulated by chronic stress in male rats" in 22nd European Congress of Endocrinology; 2020 Sep 5-9 (2020):AEP435,
https://doi.org/10.1530/endoabs.70.AEP435 . .

TY  - CONF
AU  - Gligorovska, Ljupka
AU  - Ljumović, Kristina
AU  - Ignjatović, Đurđica
AU  - Tovilović-Kovačević, Gordana
AU  - Đorđević, Ana
PY  - 2020
UR  - https://sites.google.com/view/costmeetingbelgrade/home
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3992
AB  - Modern lifestyle, characterized by increased consumption of fructose-enriched beverages, can lead to obesity, type 2 diabetes and cardiovascular diseases. Since increased fructose intake is often associated with chronic low-grade inflammation and increased oxidative stress in various tissues, the aim was to investigate the level of inflammation and antioxidant protection in endothelial, neuroblastoma and preadipocyte cell lines treated with fructose. We examined the effects of 4-hour treatment with different concentrations of fructose (0.5 mM, 2.5 mM and 10 mM) on gene expression of pro-inflammatory cytokines (tumor necrosis factor α (TNFα), interleukin (IL) 1β and 6) in endothelial (EA.hy926), neuroblastoma (SH-SY5Y) and differentiated preadipocyte (3T3-F442A) cells. The protein levels of nuclear factor-κB (NF-κB), IκB, superoxide dismutase (SOD) 1 and 2, catalase, glutathione reductase and glutathione S-transferase, were also analyzed. In endothelial cells, 0.5 mM and 2.5 mM fructose treatment caused significant increase of TNFα mRNA level, while in SH-SY5Y and differentiated 3T3-F442A cells, IL-6 mRNA level was elevated after 0.5 mM fructose treatment. Although fructose increased pro-inflammatory cytokines in cell-type and dose-specific manner, decreased IκB protein level was detected only in adipocytes regardless of the dose. Finally, among all examined antioxidant enzymes, only SOD2 was significantly reduced in all cell types upon 2.5 mM fructose treatment. These preliminary results show that the effects of fructose on inflammation and antioxidant enzymes are both cell-type and dose specific. A marked decrease in the levels of SOD2, observed in all examined cells, can be associated with lower antioxidative defense under moderate fructose concentration.
PB  - University of Belgrade: Faculty of Pharmacy
C3  - Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts
T1  - Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment
SP  - 36
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3992
ER  - 

@conference{
author = "Gligorovska, Ljupka and Ljumović, Kristina and Ignjatović, Đurđica and Tovilović-Kovačević, Gordana and Đorđević, Ana",
year = "2020",
abstract = "Modern lifestyle, characterized by increased consumption of fructose-enriched beverages, can lead to obesity, type 2 diabetes and cardiovascular diseases. Since increased fructose intake is often associated with chronic low-grade inflammation and increased oxidative stress in various tissues, the aim was to investigate the level of inflammation and antioxidant protection in endothelial, neuroblastoma and preadipocyte cell lines treated with fructose. We examined the effects of 4-hour treatment with different concentrations of fructose (0.5 mM, 2.5 mM and 10 mM) on gene expression of pro-inflammatory cytokines (tumor necrosis factor α (TNFα), interleukin (IL) 1β and 6) in endothelial (EA.hy926), neuroblastoma (SH-SY5Y) and differentiated preadipocyte (3T3-F442A) cells. The protein levels of nuclear factor-κB (NF-κB), IκB, superoxide dismutase (SOD) 1 and 2, catalase, glutathione reductase and glutathione S-transferase, were also analyzed. In endothelial cells, 0.5 mM and 2.5 mM fructose treatment caused significant increase of TNFα mRNA level, while in SH-SY5Y and differentiated 3T3-F442A cells, IL-6 mRNA level was elevated after 0.5 mM fructose treatment. Although fructose increased pro-inflammatory cytokines in cell-type and dose-specific manner, decreased IκB protein level was detected only in adipocytes regardless of the dose. Finally, among all examined antioxidant enzymes, only SOD2 was significantly reduced in all cell types upon 2.5 mM fructose treatment. These preliminary results show that the effects of fructose on inflammation and antioxidant enzymes are both cell-type and dose specific. A marked decrease in the levels of SOD2, observed in all examined cells, can be associated with lower antioxidative defense under moderate fructose concentration.",
publisher = "University of Belgrade: Faculty of Pharmacy",
journal = "Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts",
title = "Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment",
pages = "36",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3992"
}

Gligorovska, L., Ljumović, K., Ignjatović, Đ., Tovilović-Kovačević, G.,& Đorđević, A.. (2020). Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment. in Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts
University of Belgrade: Faculty of Pharmacy., 36.
https://hdl.handle.net/21.15107/rcub_ibiss_3992

Gligorovska L, Ljumović K, Ignjatović Đ, Tovilović-Kovačević G, Đorđević A. Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment. in Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts. 2020;:36.
https://hdl.handle.net/21.15107/rcub_ibiss_3992 .

Gligorovska, Ljupka, Ljumović, Kristina, Ignjatović, Đurđica, Tovilović-Kovačević, Gordana, Đorđević, Ana, "Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment" in Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts (2020):36,
https://hdl.handle.net/21.15107/rcub_ibiss_3992 .

TY  - JOUR
AU  - Romić, Snježana
AU  - Đorđević, Ana
AU  - Tepavčević, Snežana
AU  - Ćulafić, Tijana
AU  - Stojiljković, Mojca
AU  - Bursać, Biljana
AU  - Stanišić, Jelena
AU  - Kostić, Milan
AU  - Gligorovska, Ljupka
AU  - Korićanac, Goran
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/31974538
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3629
AB  - Both a diet rich in fructose and chronic stress exposure induce metabolic and cardiovascular disturbances. The aim of this study was to examine the effects of the fructose-rich diet and chronic stress, separately and in combination, on insulin signaling and molecules regulating glycogen synthesis and ion transport in the heart, and to reveal whether these effects coincide with changes in glucocorticoid receptor (GR) activation. Male Wistar rats were subjected to 10% fructose in drinking water and/or to chronic unpredictable stress for 9 weeks. Protein expression and/or phosphorylation of the insulin receptor (IR), protein tyrosine phosphatase 1B, insulin receptor substrate 1 (IRS1), protein kinase B (Akt), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase-3β (GSK-3β) and Na+/K+-ATPase α-subunits in cardiac tissue were analyzed by western blot. GR distribution between cytosolic and nuclear fractions was also analyzed. The fructose-rich diet decreased the level of pERK1/2 (Thr202/Tyr204) and pGSK-3β (Ser9) independently of stress, while chronic stress increased the IRS1 content and prevented the fructose diet-induced decrease of the pAkt (Ser473) level. The fructose-rich diet in combination with chronic stress reduced the protein content of cardiac IR and attenuated IRS1 upregulation. Separate treatments increased the protein content of Na+/K+-ATPase α1- and α2-subunits, while after combined treatment the α2 content was at the control level and the α1 content was lower than the control level. The effect of combined treatment on cardiac IR and α2-subunit expression could be mediated by increased GR nuclear accumulation. Our study provides new insights into the effects of chronic stress and a combination of the fructose diet and chronic stress on the studied molecules in the heart.
T2  - Food and Function
T1  - Effects of a fructose-rich diet and chronic stress on insulin signaling and regulation of glycogen synthase kinase-3 beta and the sodium-potassium pump in the hearts of male rats.
IS  - 2
VL  - 11
DO  - 10.1039/c9fo02306b
SP  - 1455
EP  - 1466
ER  - 

@article{
author = "Romić, Snježana and Đorđević, Ana and Tepavčević, Snežana and Ćulafić, Tijana and Stojiljković, Mojca and Bursać, Biljana and Stanišić, Jelena and Kostić, Milan and Gligorovska, Ljupka and Korićanac, Goran",
year = "2020",
abstract = "Both a diet rich in fructose and chronic stress exposure induce metabolic and cardiovascular disturbances. The aim of this study was to examine the effects of the fructose-rich diet and chronic stress, separately and in combination, on insulin signaling and molecules regulating glycogen synthesis and ion transport in the heart, and to reveal whether these effects coincide with changes in glucocorticoid receptor (GR) activation. Male Wistar rats were subjected to 10% fructose in drinking water and/or to chronic unpredictable stress for 9 weeks. Protein expression and/or phosphorylation of the insulin receptor (IR), protein tyrosine phosphatase 1B, insulin receptor substrate 1 (IRS1), protein kinase B (Akt), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase-3β (GSK-3β) and Na+/K+-ATPase α-subunits in cardiac tissue were analyzed by western blot. GR distribution between cytosolic and nuclear fractions was also analyzed. The fructose-rich diet decreased the level of pERK1/2 (Thr202/Tyr204) and pGSK-3β (Ser9) independently of stress, while chronic stress increased the IRS1 content and prevented the fructose diet-induced decrease of the pAkt (Ser473) level. The fructose-rich diet in combination with chronic stress reduced the protein content of cardiac IR and attenuated IRS1 upregulation. Separate treatments increased the protein content of Na+/K+-ATPase α1- and α2-subunits, while after combined treatment the α2 content was at the control level and the α1 content was lower than the control level. The effect of combined treatment on cardiac IR and α2-subunit expression could be mediated by increased GR nuclear accumulation. Our study provides new insights into the effects of chronic stress and a combination of the fructose diet and chronic stress on the studied molecules in the heart.",
journal = "Food and Function",
title = "Effects of a fructose-rich diet and chronic stress on insulin signaling and regulation of glycogen synthase kinase-3 beta and the sodium-potassium pump in the hearts of male rats.",
number = "2",
volume = "11",
doi = "10.1039/c9fo02306b",
pages = "1455-1466"
}

Romić, S., Đorđević, A., Tepavčević, S., Ćulafić, T., Stojiljković, M., Bursać, B., Stanišić, J., Kostić, M., Gligorovska, L.,& Korićanac, G.. (2020). Effects of a fructose-rich diet and chronic stress on insulin signaling and regulation of glycogen synthase kinase-3 beta and the sodium-potassium pump in the hearts of male rats.. in Food and Function, 11(2), 1455-1466.
https://doi.org/10.1039/c9fo02306b

Romić S, Đorđević A, Tepavčević S, Ćulafić T, Stojiljković M, Bursać B, Stanišić J, Kostić M, Gligorovska L, Korićanac G. Effects of a fructose-rich diet and chronic stress on insulin signaling and regulation of glycogen synthase kinase-3 beta and the sodium-potassium pump in the hearts of male rats.. in Food and Function. 2020;11(2):1455-1466.
doi:10.1039/c9fo02306b .

Romić, Snježana, Đorđević, Ana, Tepavčević, Snežana, Ćulafić, Tijana, Stojiljković, Mojca, Bursać, Biljana, Stanišić, Jelena, Kostić, Milan, Gligorovska, Ljupka, Korićanac, Goran, "Effects of a fructose-rich diet and chronic stress on insulin signaling and regulation of glycogen synthase kinase-3 beta and the sodium-potassium pump in the hearts of male rats." in Food and Function, 11, no. 2 (2020):1455-1466,
https://doi.org/10.1039/c9fo02306b . .

TY  - CONF
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Brkljačić, Jelena
AU  - Teofilović, Ana
AU  - Bursać, Biljana
AU  - Radovanović, Marina
AU  - Gligorovska, Ljupka
AU  - Kovačević, Sanja
AU  - Matić, Gordana
AU  - Đorđević, Ana
PY  - 2019
UR  - https://www.isos.rs/congress-2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3991
AB  - Fructose overconsumption, especially in the form of sweetened beverages, has been linked to development of obesity, insulin resistance, dyslipidemia and type 2 diabetes. In rodents, high-fructose diet leads to hypertriglyceridemia, ectopic fat deposition and insulin resistance. Metabolically triggered inflammation (metaflammation) is now recognized as a link between nutrient signals and insulin resistance and considered as usual suspect for metabolic disturbances. Metaflammation usually evolve from visceral adipose tissue, progresses to liver and brain strucures, and results in peripheral insulin resistance, lipid accumulation and oxidative stress. Hence, the aim of our study was to investigate metaflammation as a trigger for fructose-induced metabolic disturbances. Experiments were performed on male Wistar rats fed with different concentrations of liquid fructose (10, 20 and 60%) during 9 weeks. Physiological and biochemical parameters, hepatic and brain inflammation, indicators of peripheral and systemic insulin resistance, as well as hepatic lipogenesis and oxidative stress were examined. The results demonstrated that fructose-enriched diet generally led to increased proinflamatory cytokines in the liver, hippocampus and hypothalamus, and to stimulated activation of proinflamatory kinases NFκB and JNK, while it did not change the expression of inflammasome component NLRP3, toll-like receptor 4 or anti-inflammatory cytokines in the liver. The observed metabolic inflammation was accompanied with impaired glucose tolerance after 10 and 20% fructose-enriched diet, while decreased hepatic insulin sensitivity, hypetriglyceridemia and increased expression of hepatic lipogenic genes were observed after all fructose diets. The treatment of fructose-fed rats with chronic unpredictable stress annulled the effects of fructose on hepatic and hypothalamic inflammation and glucose tolerance, but did not alter fructose-induced effects on lipogenesis and insulin signaling. The results suggest that fructose-induced metaflammation and systemic insulin resistance are closely interconnected, while the link between inflammation and other metabolic disturbances could still be a matter of debate.
PB  - Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade
PB  - Immunological Society of Serbia
C3  - Immunology at the Confluence of Multidisciplinary Approaches : abstract book
T1  - Is Metaflammation a Usual Suspect for Fructose-induced Metabolic Disturbances?
SP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3991
ER  - 

@conference{
author = "Veličković, Nataša and Vojnović-Milutinović, Danijela and Brkljačić, Jelena and Teofilović, Ana and Bursać, Biljana and Radovanović, Marina and Gligorovska, Ljupka and Kovačević, Sanja and Matić, Gordana and Đorđević, Ana",
year = "2019",
abstract = "Fructose overconsumption, especially in the form of sweetened beverages, has been linked to development of obesity, insulin resistance, dyslipidemia and type 2 diabetes. In rodents, high-fructose diet leads to hypertriglyceridemia, ectopic fat deposition and insulin resistance. Metabolically triggered inflammation (metaflammation) is now recognized as a link between nutrient signals and insulin resistance and considered as usual suspect for metabolic disturbances. Metaflammation usually evolve from visceral adipose tissue, progresses to liver and brain strucures, and results in peripheral insulin resistance, lipid accumulation and oxidative stress. Hence, the aim of our study was to investigate metaflammation as a trigger for fructose-induced metabolic disturbances. Experiments were performed on male Wistar rats fed with different concentrations of liquid fructose (10, 20 and 60%) during 9 weeks. Physiological and biochemical parameters, hepatic and brain inflammation, indicators of peripheral and systemic insulin resistance, as well as hepatic lipogenesis and oxidative stress were examined. The results demonstrated that fructose-enriched diet generally led to increased proinflamatory cytokines in the liver, hippocampus and hypothalamus, and to stimulated activation of proinflamatory kinases NFκB and JNK, while it did not change the expression of inflammasome component NLRP3, toll-like receptor 4 or anti-inflammatory cytokines in the liver. The observed metabolic inflammation was accompanied with impaired glucose tolerance after 10 and 20% fructose-enriched diet, while decreased hepatic insulin sensitivity, hypetriglyceridemia and increased expression of hepatic lipogenic genes were observed after all fructose diets. The treatment of fructose-fed rats with chronic unpredictable stress annulled the effects of fructose on hepatic and hypothalamic inflammation and glucose tolerance, but did not alter fructose-induced effects on lipogenesis and insulin signaling. The results suggest that fructose-induced metaflammation and systemic insulin resistance are closely interconnected, while the link between inflammation and other metabolic disturbances could still be a matter of debate.",
publisher = "Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Immunological Society of Serbia",
journal = "Immunology at the Confluence of Multidisciplinary Approaches : abstract book",
title = "Is Metaflammation a Usual Suspect for Fructose-induced Metabolic Disturbances?",
pages = "51",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3991"
}

Veličković, N., Vojnović-Milutinović, D., Brkljačić, J., Teofilović, A., Bursać, B., Radovanović, M., Gligorovska, L., Kovačević, S., Matić, G.,& Đorđević, A.. (2019). Is Metaflammation a Usual Suspect for Fructose-induced Metabolic Disturbances?. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book
Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade., 51.
https://hdl.handle.net/21.15107/rcub_ibiss_3991

Veličković N, Vojnović-Milutinović D, Brkljačić J, Teofilović A, Bursać B, Radovanović M, Gligorovska L, Kovačević S, Matić G, Đorđević A. Is Metaflammation a Usual Suspect for Fructose-induced Metabolic Disturbances?. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book. 2019;:51.
https://hdl.handle.net/21.15107/rcub_ibiss_3991 .

Veličković, Nataša, Vojnović-Milutinović, Danijela, Brkljačić, Jelena, Teofilović, Ana, Bursać, Biljana, Radovanović, Marina, Gligorovska, Ljupka, Kovačević, Sanja, Matić, Gordana, Đorđević, Ana, "Is Metaflammation a Usual Suspect for Fructose-induced Metabolic Disturbances?" in Immunology at the Confluence of Multidisciplinary Approaches : abstract book (2019):51,
https://hdl.handle.net/21.15107/rcub_ibiss_3991 .

TY  - CONF
AU  - Gligorovska, Ljupka
AU  - Teofilović, Ana
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Kovačević, Sanja
AU  - Matić, Gordana
AU  - Đorđević, Ana
PY  - 2019
UR  - https://www.faobmbkl2019.com/abstract-book
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3993
AB  - The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in metabolic inflammation and regulation of energy metabolism in the liver. Genetic deletion of Mif may contribute to the development of systemic insulin resistance, while fructose overload can disturb hepatic lipid metabolism leading to steatosis, inflammation and type 2 diabetes. The aim of the present study was to elucidate the impact of combined effects of Mif deficiency and fructose-enriched diet on insulin sensitivity and lipid metabolism in the liver of male mice. We analysed the effects of 9-week 20 % fructose-enriched diet on indicators of systemic insulin sensitivity, liver histology and biochemical parameters of lipid metabolism in wild type and MIF deficient (MIF−/−) C57Bl/6J mice. The expression of the following lipogenic genes was examined: fatty acid synthase (Fas), acetyl-CoA carboxylase (Acc) and stearoyl-CoA desaturase-1 (Scd1). Levels of insulin-regulated transcriptional factors involved in lipogenesis (sterol regulatory element-binding protein-1c, SREBP-1c and carbohydrate-response element-binding protein, ChREBP), together with the expression of hepatic fatty acid metabolism regulator (peroxisome-proliferator-activated receptor α, PPARα) were also analysed. Mif deficiency did not affect plasma free fatty acid and triglyceride levels, but impaired systemic insulin sensitivity regardless of the diet. In MIF−/− animals, liver histological analysis confirmed the presence of lipid droplets and focal necrosis, but these effects were more pronounced in MIF−/− mice on fructose diet. Although Acc and Fas levels were unchanged, elevated levels of Scd1, SREBP-1c and ChREBP, together with decreased PPARα protein level, were most likely responsible for the lipid accumulation observed in the liver of MIF−/− animals. In conclusion, the results show that energy-rich fructose diet potentiates the effects of Mif deficiency on development of fatty liver and systemic insulin resistance.
PB  - Malaysian Society for Biochemistry and Molecular Biology
PB  - Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB)
PB  - The International Union of Biochemistry and Molecular Biology (IUBMB)
C3  - Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP), Abstract Book
T1  - Effects of Mif deficiency and fructose-enriched diet on lipid metabolism in the mouse liver
SP  - 39
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3993
ER  - 

@conference{
author = "Gligorovska, Ljupka and Teofilović, Ana and Veličković, Nataša and Vojnović-Milutinović, Danijela and Kovačević, Sanja and Matić, Gordana and Đorđević, Ana",
year = "2019",
abstract = "The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in metabolic inflammation and regulation of energy metabolism in the liver. Genetic deletion of Mif may contribute to the development of systemic insulin resistance, while fructose overload can disturb hepatic lipid metabolism leading to steatosis, inflammation and type 2 diabetes. The aim of the present study was to elucidate the impact of combined effects of Mif deficiency and fructose-enriched diet on insulin sensitivity and lipid metabolism in the liver of male mice. We analysed the effects of 9-week 20 % fructose-enriched diet on indicators of systemic insulin sensitivity, liver histology and biochemical parameters of lipid metabolism in wild type and MIF deficient (MIF−/−) C57Bl/6J mice. The expression of the following lipogenic genes was examined: fatty acid synthase (Fas), acetyl-CoA carboxylase (Acc) and stearoyl-CoA desaturase-1 (Scd1). Levels of insulin-regulated transcriptional factors involved in lipogenesis (sterol regulatory element-binding protein-1c, SREBP-1c and carbohydrate-response element-binding protein, ChREBP), together with the expression of hepatic fatty acid metabolism regulator (peroxisome-proliferator-activated receptor α, PPARα) were also analysed. Mif deficiency did not affect plasma free fatty acid and triglyceride levels, but impaired systemic insulin sensitivity regardless of the diet. In MIF−/− animals, liver histological analysis confirmed the presence of lipid droplets and focal necrosis, but these effects were more pronounced in MIF−/− mice on fructose diet. Although Acc and Fas levels were unchanged, elevated levels of Scd1, SREBP-1c and ChREBP, together with decreased PPARα protein level, were most likely responsible for the lipid accumulation observed in the liver of MIF−/− animals. In conclusion, the results show that energy-rich fructose diet potentiates the effects of Mif deficiency on development of fatty liver and systemic insulin resistance.",
publisher = "Malaysian Society for Biochemistry and Molecular Biology, Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB), The International Union of Biochemistry and Molecular Biology (IUBMB)",
journal = "Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP), Abstract Book",
title = "Effects of Mif deficiency and fructose-enriched diet on lipid metabolism in the mouse liver",
pages = "39",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3993"
}

Gligorovska, L., Teofilović, A., Veličković, N., Vojnović-Milutinović, D., Kovačević, S., Matić, G.,& Đorđević, A.. (2019). Effects of Mif deficiency and fructose-enriched diet on lipid metabolism in the mouse liver. in Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP), Abstract Book
Malaysian Society for Biochemistry and Molecular Biology., 39.
https://hdl.handle.net/21.15107/rcub_ibiss_3993

Gligorovska L, Teofilović A, Veličković N, Vojnović-Milutinović D, Kovačević S, Matić G, Đorđević A. Effects of Mif deficiency and fructose-enriched diet on lipid metabolism in the mouse liver. in Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP), Abstract Book. 2019;:39.
https://hdl.handle.net/21.15107/rcub_ibiss_3993 .

Gligorovska, Ljupka, Teofilović, Ana, Veličković, Nataša, Vojnović-Milutinović, Danijela, Kovačević, Sanja, Matić, Gordana, Đorđević, Ana, "Effects of Mif deficiency and fructose-enriched diet on lipid metabolism in the mouse liver" in Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP), Abstract Book (2019):39,
https://hdl.handle.net/21.15107/rcub_ibiss_3993 .

TY  - CONF
AU  - Gligorovska, Ljupka
AU  - Teofilović, Ana
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Kovačević, Sanja
AU  - Matić, Gordana
AU  - Đorđević, Ana
PY  - 2019
UR  - https://www.isos.rs/congress-2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3990
AB  - Introduction: The macrophage migration inhibitory factor (MIF) is a key pro-inflammatory mediator involved in the regulation of energy metabolism and metabolic inflammation in the liver. Fructose overconsumption has been previously associated with development of low-grade inflammation characterized by elevated production of pro-inflammatory cytokines and activation of mitogen-activated protein kinase (MAPK) signaling pathway. The inflammatory response can disrupt insulin signaling and genetic deletion of Mif may contribute to the development of systemic insulin resistance, as well. The aim: The aim of the present study was to elucidate combined effects of Mif deficiency and fructose-enriched diet on metabolic inflammation and insulin sensitivity in the liver of male mice. Methods: Wild type (WT) and Mif deficient (MIF−/−) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on indicators of insulin sensitivity and markers of metabolic inflammation (tumor necrosis factor α (TNFα), interleukin (IL)-1β and IL-6). Deregulation of Akt signaling pathway was used as hallmark of hepatic insulin resistance. Also, the protein levels of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase 1 (JNK) and p38 were analyzed. Results: Mif deficient animals exibited elevated expression of IL-1β and IL-6 in the liver, regardless of the diet regime, while hepatic TNFα was unchanged in all animals. On the other hand, both total and phosphorylated ERK and JNK protein levels were decreased in all fructose-fed mice. In the same animals, impaired hepatic insulin signaling, revealed by decreased pAkt and total Akt protein levels, was observed. Conclusion: Although, Mif deficiency led to upregulation of pro-inflammatory cytokines, fructose diet did not aggravate this effect. On the other hand, insulin signalling was diminished by fructose feding independently of Mif deficiency.
PB  - Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade
PB  - Immunological Society of Serbia
C3  - Immunology At The Confluence of Multidisciplinary Approaches
T1  - Inflammation and Insulin Sensitivity in The Liver of Fructose-fed Mif Deficient Mice
SP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3990
ER  - 

@conference{
author = "Gligorovska, Ljupka and Teofilović, Ana and Veličković, Nataša and Vojnović-Milutinović, Danijela and Kovačević, Sanja and Matić, Gordana and Đorđević, Ana",
year = "2019",
abstract = "Introduction: The macrophage migration inhibitory factor (MIF) is a key pro-inflammatory mediator involved in the regulation of energy metabolism and metabolic inflammation in the liver. Fructose overconsumption has been previously associated with development of low-grade inflammation characterized by elevated production of pro-inflammatory cytokines and activation of mitogen-activated protein kinase (MAPK) signaling pathway. The inflammatory response can disrupt insulin signaling and genetic deletion of Mif may contribute to the development of systemic insulin resistance, as well. The aim: The aim of the present study was to elucidate combined effects of Mif deficiency and fructose-enriched diet on metabolic inflammation and insulin sensitivity in the liver of male mice. Methods: Wild type (WT) and Mif deficient (MIF−/−) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on indicators of insulin sensitivity and markers of metabolic inflammation (tumor necrosis factor α (TNFα), interleukin (IL)-1β and IL-6). Deregulation of Akt signaling pathway was used as hallmark of hepatic insulin resistance. Also, the protein levels of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase 1 (JNK) and p38 were analyzed. Results: Mif deficient animals exibited elevated expression of IL-1β and IL-6 in the liver, regardless of the diet regime, while hepatic TNFα was unchanged in all animals. On the other hand, both total and phosphorylated ERK and JNK protein levels were decreased in all fructose-fed mice. In the same animals, impaired hepatic insulin signaling, revealed by decreased pAkt and total Akt protein levels, was observed. Conclusion: Although, Mif deficiency led to upregulation of pro-inflammatory cytokines, fructose diet did not aggravate this effect. On the other hand, insulin signalling was diminished by fructose feding independently of Mif deficiency.",
publisher = "Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Immunological Society of Serbia",
journal = "Immunology At The Confluence of Multidisciplinary Approaches",
title = "Inflammation and Insulin Sensitivity in The Liver of Fructose-fed Mif Deficient Mice",
pages = "53",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3990"
}

Gligorovska, L., Teofilović, A., Veličković, N., Vojnović-Milutinović, D., Kovačević, S., Matić, G.,& Đorđević, A.. (2019). Inflammation and Insulin Sensitivity in The Liver of Fructose-fed Mif Deficient Mice. in Immunology At The Confluence of Multidisciplinary Approaches
Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade., 53.
https://hdl.handle.net/21.15107/rcub_ibiss_3990

Gligorovska L, Teofilović A, Veličković N, Vojnović-Milutinović D, Kovačević S, Matić G, Đorđević A. Inflammation and Insulin Sensitivity in The Liver of Fructose-fed Mif Deficient Mice. in Immunology At The Confluence of Multidisciplinary Approaches. 2019;:53.
https://hdl.handle.net/21.15107/rcub_ibiss_3990 .

Gligorovska, Ljupka, Teofilović, Ana, Veličković, Nataša, Vojnović-Milutinović, Danijela, Kovačević, Sanja, Matić, Gordana, Đorđević, Ana, "Inflammation and Insulin Sensitivity in The Liver of Fructose-fed Mif Deficient Mice" in Immunology At The Confluence of Multidisciplinary Approaches (2019):53,
https://hdl.handle.net/21.15107/rcub_ibiss_3990 .

TY  - CONF
AU  - Đorđević, Ana
AU  - Vujković Cvijin, Ivan I.
AU  - Lešović, Snežana J.
AU  - Gligorovska, Ljupka
AU  - Bursać, Biljana
AU  - Vojnović-Milutinović, Danijela
AU  - Matić, Gordana
PY  - 2019
UR  - https://blog.u-bourgogne.fr/cost-nutredox/wp-content/uploads/sites/81/2019/09/20191002-Lisbon-Abstract-book-vf-min.pdf
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3994
AB  - Prevalence  of  obesity  among  adolescents  has  been  constantly  increasing  in  the  last decades. The  treatment  of  obesity  requires  multidisciplinary  approach,  which  includes dietary management. However, not all people respond to dietary intervention in the same way. Since gut microbiota has been tightly linked to obesity, the aim of this pilot study was to assess whether microbiota composition affects the outcome of the hypocaloric diet on weight loss in obese male adolescents.Forty-four obese male adolescents(average BMI>95thpercentile), 12-15 years old, were selected  from  the  large  cohort  of  500  patients.  Their  body  composition  was  assessed before  and  after  3-week  balanced  hypocaloric  diet  (1200-1700  kcal)  with  preserved nutritional  value.    Microbial  DNA  was  extracted  from  cryopreserved  fecal  samples collected before the dietary intervention. Alterations of the gut microbiota were analyzed using MiSeq 16S rRNA gene sequencing. The primary outcome of the diet was the change in body weight and BMI. Subjects were divided  in  2  groups  according  to  significant  differences  in  delta  BMI  after  the  dietary intervention (P< 0.001). The values for delta BMIs were 1.93 and 2.66 for groups 1 and 2,  respectively.  The  observed  differences  were  associated  with  fecal  microbiome composition.  Group  2  subjects,  which  have  lost  more  weight,  originally  had  less Firmicutes   spp. bacteria,   more   specifically   from   families Lachnospiraceae and Desulfovibrionaceae. These  preliminary  results  show  that  the  ability  for  diet-induced  weight  loss  could  be associated   with   microbiota   composition.   Whether   certain   bacterial   taxa   represent facilitating or  resilience  factor  for  weight  loss  is  yet  to  be  determined  in  future experiments.
PB  - COST (European Cooperation in Science and Technology), NutRedox COST Action CA 16112
PB  - Universidade Lusófona
C3  - Lisbon, Portugal: NutRedox COST (European Cooperation in Science and Technology) Action CA 16112 Abstract Book
T1  - Gut Microbiota Composition Influences the Extent of Weight Loss After Hypocaloric Diet in Obese Male Adolescents
SP  - 36
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3994
ER  - 

@conference{
author = "Đorđević, Ana and Vujković Cvijin, Ivan I. and Lešović, Snežana J. and Gligorovska, Ljupka and Bursać, Biljana and Vojnović-Milutinović, Danijela and Matić, Gordana",
year = "2019",
abstract = "Prevalence  of  obesity  among  adolescents  has  been  constantly  increasing  in  the  last decades. The  treatment  of  obesity  requires  multidisciplinary  approach,  which  includes dietary management. However, not all people respond to dietary intervention in the same way. Since gut microbiota has been tightly linked to obesity, the aim of this pilot study was to assess whether microbiota composition affects the outcome of the hypocaloric diet on weight loss in obese male adolescents.Forty-four obese male adolescents(average BMI>95thpercentile), 12-15 years old, were selected  from  the  large  cohort  of  500  patients.  Their  body  composition  was  assessed before  and  after  3-week  balanced  hypocaloric  diet  (1200-1700  kcal)  with  preserved nutritional  value.    Microbial  DNA  was  extracted  from  cryopreserved  fecal  samples collected before the dietary intervention. Alterations of the gut microbiota were analyzed using MiSeq 16S rRNA gene sequencing. The primary outcome of the diet was the change in body weight and BMI. Subjects were divided  in  2  groups  according  to  significant  differences  in  delta  BMI  after  the  dietary intervention (P< 0.001). The values for delta BMIs were 1.93 and 2.66 for groups 1 and 2,  respectively.  The  observed  differences  were  associated  with  fecal  microbiome composition.  Group  2  subjects,  which  have  lost  more  weight,  originally  had  less Firmicutes   spp. bacteria,   more   specifically   from   families Lachnospiraceae and Desulfovibrionaceae. These  preliminary  results  show  that  the  ability  for  diet-induced  weight  loss  could  be associated   with   microbiota   composition.   Whether   certain   bacterial   taxa   represent facilitating or  resilience  factor  for  weight  loss  is  yet  to  be  determined  in  future experiments.",
publisher = "COST (European Cooperation in Science and Technology), NutRedox COST Action CA 16112, Universidade Lusófona",
journal = "Lisbon, Portugal: NutRedox COST (European Cooperation in Science and Technology) Action CA 16112 Abstract Book",
title = "Gut Microbiota Composition Influences the Extent of Weight Loss After Hypocaloric Diet in Obese Male Adolescents",
pages = "36",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3994"
}

Đorđević, A., Vujković Cvijin, I. I., Lešović, S. J., Gligorovska, L., Bursać, B., Vojnović-Milutinović, D.,& Matić, G.. (2019). Gut Microbiota Composition Influences the Extent of Weight Loss After Hypocaloric Diet in Obese Male Adolescents. in Lisbon, Portugal: NutRedox COST (European Cooperation in Science and Technology) Action CA 16112 Abstract Book
COST (European Cooperation in Science and Technology), NutRedox COST Action CA 16112., 36.
https://hdl.handle.net/21.15107/rcub_ibiss_3994

Đorđević A, Vujković Cvijin II, Lešović SJ, Gligorovska L, Bursać B, Vojnović-Milutinović D, Matić G. Gut Microbiota Composition Influences the Extent of Weight Loss After Hypocaloric Diet in Obese Male Adolescents. in Lisbon, Portugal: NutRedox COST (European Cooperation in Science and Technology) Action CA 16112 Abstract Book. 2019;:36.
https://hdl.handle.net/21.15107/rcub_ibiss_3994 .

Đorđević, Ana, Vujković Cvijin, Ivan I., Lešović, Snežana J., Gligorovska, Ljupka, Bursać, Biljana, Vojnović-Milutinović, Danijela, Matić, Gordana, "Gut Microbiota Composition Influences the Extent of Weight Loss After Hypocaloric Diet in Obese Male Adolescents" in Lisbon, Portugal: NutRedox COST (European Cooperation in Science and Technology) Action CA 16112 Abstract Book (2019):36,
https://hdl.handle.net/21.15107/rcub_ibiss_3994 .

TY  - CONF
AU  - Kovačević, Sanja
AU  - Bursać, Biljana
AU  - Đorđević, Ana
AU  - Gligorovska, Ljupka
AU  - Matić, Gordana
AU  - Elaković, Ivana
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3988
AB  - Background: Increased consumption of caloric food rich in fructose and daily exposure to unpredictable stress became hallmarks of modern lifestyle and have been associated with the development of metabolic syndrome, type2 diabetes and cardiovascular diseases1,2. Visceral  adipose  tissue  (VAT)  and  muscles are important centers of lipid and glucose metabolism and metabolic disturbances  in  these  organs  and  their crosstalk  could  vastly contribute to the development of metabolic diseases3,4. The  aim: To  elucidate  whether prolonged combination of fructose  over consumption and chronic stress disturbs lipid metabolism and insulin signaling in rat VAT and muscle. Methods: We  examined the  effects  of  9-week  fructose-enriched diet with  and  without exposure to unpredictable stress on expression of genes and level of proteins involved in lipid  uptake (lipoprotein lipase, fatty  acid  translocase  and fatty  acid transport  protein), de novo lipogenesis    (acetyl-CoA    carboxylase    and fatty    acid    synthase), lipolysis (hormone sensitive lipase and adipose   triglyceride   lipase)   and fatty   acids oxidation (carnitine  palmitoyltransferase  I)  in VAT  and muscle of  male  Wistar  rats.  Additionally, muscle  insulin  signaling  was  analyzed at the  level  of insulin receptor  substrate-1  (IRS1) and Akt kinase, and their activating and inhibitory phosphorylations. Results: Combination  of  fructose  overconsumption  and  stress increased plasma insulin and free fatty acids level, upregulated expression of both lipolytic and lipogenic genes in VAT and stimulated lipid uptake, lipolysis and β-oxidation in muscle. Furthermore, reduced protein  content  and  stimulatory  phosphorylation  of IRS1  and Akt  kinase, together  with unchanged inhibitory phosphorylation of IRS1 was observed in muscle. Conclusions: The  results show that the  combination  of fructose  over consumption and chronic stress disturbs lipid metabolism in VAT and muscle. Importantly, upregulated VAT lipolysis  elevates  plasma  free  fatty  acids, which  intensify their  influx  to  muscles  possibly leading to muscle insulin resistance detected in fructose fed stressed rats.
PB  - EMBO Press
C3  - EMBO Workshop Organ crosstalk in energy balance and metabolic disease; 2019 Apr 8-11; Sancti Petri, Chiclana, Cádiz, Spain
T1  - Combination Of Fructose And Stress Induces Insulin Resistance And Disturbs Lipid Metabolism In Muscle And Adipose Tissue Of Rats
SP  - 45
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3988
ER  - 

@conference{
author = "Kovačević, Sanja and Bursać, Biljana and Đorđević, Ana and Gligorovska, Ljupka and Matić, Gordana and Elaković, Ivana",
year = "2019",
abstract = "Background: Increased consumption of caloric food rich in fructose and daily exposure to unpredictable stress became hallmarks of modern lifestyle and have been associated with the development of metabolic syndrome, type2 diabetes and cardiovascular diseases1,2. Visceral  adipose  tissue  (VAT)  and  muscles are important centers of lipid and glucose metabolism and metabolic disturbances  in  these  organs  and  their crosstalk  could  vastly contribute to the development of metabolic diseases3,4. The  aim: To  elucidate  whether prolonged combination of fructose  over consumption and chronic stress disturbs lipid metabolism and insulin signaling in rat VAT and muscle. Methods: We  examined the  effects  of  9-week  fructose-enriched diet with  and  without exposure to unpredictable stress on expression of genes and level of proteins involved in lipid  uptake (lipoprotein lipase, fatty  acid  translocase  and fatty  acid transport  protein), de novo lipogenesis    (acetyl-CoA    carboxylase    and fatty    acid    synthase), lipolysis (hormone sensitive lipase and adipose   triglyceride   lipase)   and fatty   acids oxidation (carnitine  palmitoyltransferase  I)  in VAT  and muscle of  male  Wistar  rats.  Additionally, muscle  insulin  signaling  was  analyzed at the  level  of insulin receptor  substrate-1  (IRS1) and Akt kinase, and their activating and inhibitory phosphorylations. Results: Combination  of  fructose  overconsumption  and  stress increased plasma insulin and free fatty acids level, upregulated expression of both lipolytic and lipogenic genes in VAT and stimulated lipid uptake, lipolysis and β-oxidation in muscle. Furthermore, reduced protein  content  and  stimulatory  phosphorylation  of IRS1  and Akt  kinase, together  with unchanged inhibitory phosphorylation of IRS1 was observed in muscle. Conclusions: The  results show that the  combination  of fructose  over consumption and chronic stress disturbs lipid metabolism in VAT and muscle. Importantly, upregulated VAT lipolysis  elevates  plasma  free  fatty  acids, which  intensify their  influx  to  muscles  possibly leading to muscle insulin resistance detected in fructose fed stressed rats.",
publisher = "EMBO Press",
journal = "EMBO Workshop Organ crosstalk in energy balance and metabolic disease; 2019 Apr 8-11; Sancti Petri, Chiclana, Cádiz, Spain",
title = "Combination Of Fructose And Stress Induces Insulin Resistance And Disturbs Lipid Metabolism In Muscle And Adipose Tissue Of Rats",
pages = "45",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3988"
}

Kovačević, S., Bursać, B., Đorđević, A., Gligorovska, L., Matić, G.,& Elaković, I.. (2019). Combination Of Fructose And Stress Induces Insulin Resistance And Disturbs Lipid Metabolism In Muscle And Adipose Tissue Of Rats. in EMBO Workshop Organ crosstalk in energy balance and metabolic disease; 2019 Apr 8-11; Sancti Petri, Chiclana, Cádiz, Spain
EMBO Press., 45.
https://hdl.handle.net/21.15107/rcub_ibiss_3988

Kovačević S, Bursać B, Đorđević A, Gligorovska L, Matić G, Elaković I. Combination Of Fructose And Stress Induces Insulin Resistance And Disturbs Lipid Metabolism In Muscle And Adipose Tissue Of Rats. in EMBO Workshop Organ crosstalk in energy balance and metabolic disease; 2019 Apr 8-11; Sancti Petri, Chiclana, Cádiz, Spain. 2019;:45.
https://hdl.handle.net/21.15107/rcub_ibiss_3988 .

Kovačević, Sanja, Bursać, Biljana, Đorđević, Ana, Gligorovska, Ljupka, Matić, Gordana, Elaković, Ivana, "Combination Of Fructose And Stress Induces Insulin Resistance And Disturbs Lipid Metabolism In Muscle And Adipose Tissue Of Rats" in EMBO Workshop Organ crosstalk in energy balance and metabolic disease; 2019 Apr 8-11; Sancti Petri, Chiclana, Cádiz, Spain (2019):45,
https://hdl.handle.net/21.15107/rcub_ibiss_3988 .

TY  - JOUR
AU  - Gligorovska, Ljupka
AU  - Bursać, Biljana
AU  - Kovačević, Sanja
AU  - Veličković, Nataša
AU  - Matić, Gordana
AU  - Đorđević, Ana
PY  - 2019
UR  - https://joe.bioscientifica.com/view/journals/joe/240/2/JOE-18-0333.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3240
AB  - The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in inflammation, regulation of energy metabolism and glucocorticoid action. Chronic low-grade inflammation may be caused by fructose intake, contributing to visceral adipose tissue (VAT) dysfunction. Since MIF is a known antagonist of glucocorticoid signaling, and deregulated glucocorticoid signaling can contribute to lipid metabolism disturbances, we hypothesized that altered MIF signaling might underlie fructose-induced adiposity through glucocorticoid action. We analyzed physiological and biochemical parameters, adipose tissue histology, insulin sensitivity and lipid metabolism in wild type and MIF-/- C57Bl/6J mice consuming 20% fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and glucocorticoid receptor (GR) protein level were examined in VAT, together with the expression of glucocorticoid-target genes involved in lipid metabolism. The expression of adipogenic and lipogenic transcriptional regulators peroxisome proliferator activated receptor gamma (PPARG) and sterol regulatory element-binding protein 1c (SREBP1c) was also assessed. Results showed disturbed insulin sensitivity in all MIF-/- mice, regardless of the diet. Mice on fructose diet had increased energy intake, but increased visceral adiposity and enlarged adipocytes were observed only in fructose-fed MIF-/- mice. Increased VAT corticosterone level and 11 beta-hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase and GR protein levels were observed in the same animals, together with induced expression of examined lipogenic genes and accumulation of PPARG and SREBP1c. In conclusion, the results showed that dietary fructose was associated with increased visceral adiposity through activation of GR-regulated lipogenic genes, but only in the absence of MIF, which set the state of hyperinsulinemia and insulin resistance.
T2  - Journal of Endocrinology
T1  - Mif deficiency promotes adiposity in fructose-fed mice.
IS  - 2
VL  - 240
DO  - 10.1530/JOE-18-0333
SP  - 133
EP  - 145
ER  - 

@article{
author = "Gligorovska, Ljupka and Bursać, Biljana and Kovačević, Sanja and Veličković, Nataša and Matić, Gordana and Đorđević, Ana",
year = "2019",
abstract = "The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in inflammation, regulation of energy metabolism and glucocorticoid action. Chronic low-grade inflammation may be caused by fructose intake, contributing to visceral adipose tissue (VAT) dysfunction. Since MIF is a known antagonist of glucocorticoid signaling, and deregulated glucocorticoid signaling can contribute to lipid metabolism disturbances, we hypothesized that altered MIF signaling might underlie fructose-induced adiposity through glucocorticoid action. We analyzed physiological and biochemical parameters, adipose tissue histology, insulin sensitivity and lipid metabolism in wild type and MIF-/- C57Bl/6J mice consuming 20% fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and glucocorticoid receptor (GR) protein level were examined in VAT, together with the expression of glucocorticoid-target genes involved in lipid metabolism. The expression of adipogenic and lipogenic transcriptional regulators peroxisome proliferator activated receptor gamma (PPARG) and sterol regulatory element-binding protein 1c (SREBP1c) was also assessed. Results showed disturbed insulin sensitivity in all MIF-/- mice, regardless of the diet. Mice on fructose diet had increased energy intake, but increased visceral adiposity and enlarged adipocytes were observed only in fructose-fed MIF-/- mice. Increased VAT corticosterone level and 11 beta-hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase and GR protein levels were observed in the same animals, together with induced expression of examined lipogenic genes and accumulation of PPARG and SREBP1c. In conclusion, the results showed that dietary fructose was associated with increased visceral adiposity through activation of GR-regulated lipogenic genes, but only in the absence of MIF, which set the state of hyperinsulinemia and insulin resistance.",
journal = "Journal of Endocrinology",
title = "Mif deficiency promotes adiposity in fructose-fed mice.",
number = "2",
volume = "240",
doi = "10.1530/JOE-18-0333",
pages = "133-145"
}

Gligorovska, L., Bursać, B., Kovačević, S., Veličković, N., Matić, G.,& Đorđević, A.. (2019). Mif deficiency promotes adiposity in fructose-fed mice.. in Journal of Endocrinology, 240(2), 133-145.
https://doi.org/10.1530/JOE-18-0333

Gligorovska L, Bursać B, Kovačević S, Veličković N, Matić G, Đorđević A. Mif deficiency promotes adiposity in fructose-fed mice.. in Journal of Endocrinology. 2019;240(2):133-145.
doi:10.1530/JOE-18-0333 .

Gligorovska, Ljupka, Bursać, Biljana, Kovačević, Sanja, Veličković, Nataša, Matić, Gordana, Đorđević, Ana, "Mif deficiency promotes adiposity in fructose-fed mice." in Journal of Endocrinology, 240, no. 2 (2019):133-145,
https://doi.org/10.1530/JOE-18-0333 . .

TY  - JOUR
AU  - Gligorovska, Ljupka
AU  - Bursać, Biljana
AU  - Kovačević, Sanja
AU  - Veličković, Nataša
AU  - Matić, Gordana
AU  - Đorđević, Ana
PY  - 2019
UR  - https://joe.bioscientifica.com/view/journals/joe/240/2/JOE-18-0333.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3243
AB  - The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in inflammation, regulation of energy metabolism and glucocorticoid action. Chronic low-grade inflammation may be caused by fructose intake, contributing to visceral adipose tissue (VAT) dysfunction. Since MIF is a known antagonist of glucocorticoid signaling, and deregulated glucocorticoid signaling can contribute to lipid metabolism disturbances, we hypothesized that altered MIF signaling might underlie fructose-induced adiposity through glucocorticoid action. We analyzed physiological and biochemical parameters, adipose tissue histology, insulin sensitivity and lipid metabolism in wild type and MIF-/- C57Bl/6J mice consuming 20% fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and glucocorticoid receptor (GR) protein level were examined in VAT, together with the expression of glucocorticoid-target genes involved in lipid metabolism. The expression of adipogenic and lipogenic transcriptional regulators peroxisome proliferator activated receptor gamma (PPARG) and sterol regulatory element-binding protein 1c (SREBP1c) was also assessed. Results showed disturbed insulin sensitivity in all MIF-/- mice, regardless of the diet. Mice on fructose diet had increased energy intake, but increased visceral adiposity and enlarged adipocytes were observed only in fructose-fed MIF-/- mice. Increased VAT corticosterone level and 11 beta-hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase and GR protein levels were observed in the same animals, together with induced expression of examined lipogenic genes and accumulation of PPARG and SREBP1c. In conclusion, the results showed that dietary fructose was associated with increased visceral adiposity through activation of GR-regulated lipogenic genes, but only in the absence of MIF, which set the state of hyperinsulinemia and insulin resistance.
T2  - Journal of Endocrinology
T1  - Mif deficiency promotes adiposity in fructose-fed mice.
DO  - 10.1530/JOE-18-0333
ER  - 

@article{
author = "Gligorovska, Ljupka and Bursać, Biljana and Kovačević, Sanja and Veličković, Nataša and Matić, Gordana and Đorđević, Ana",
year = "2019",
abstract = "The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in inflammation, regulation of energy metabolism and glucocorticoid action. Chronic low-grade inflammation may be caused by fructose intake, contributing to visceral adipose tissue (VAT) dysfunction. Since MIF is a known antagonist of glucocorticoid signaling, and deregulated glucocorticoid signaling can contribute to lipid metabolism disturbances, we hypothesized that altered MIF signaling might underlie fructose-induced adiposity through glucocorticoid action. We analyzed physiological and biochemical parameters, adipose tissue histology, insulin sensitivity and lipid metabolism in wild type and MIF-/- C57Bl/6J mice consuming 20% fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and glucocorticoid receptor (GR) protein level were examined in VAT, together with the expression of glucocorticoid-target genes involved in lipid metabolism. The expression of adipogenic and lipogenic transcriptional regulators peroxisome proliferator activated receptor gamma (PPARG) and sterol regulatory element-binding protein 1c (SREBP1c) was also assessed. Results showed disturbed insulin sensitivity in all MIF-/- mice, regardless of the diet. Mice on fructose diet had increased energy intake, but increased visceral adiposity and enlarged adipocytes were observed only in fructose-fed MIF-/- mice. Increased VAT corticosterone level and 11 beta-hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase and GR protein levels were observed in the same animals, together with induced expression of examined lipogenic genes and accumulation of PPARG and SREBP1c. In conclusion, the results showed that dietary fructose was associated with increased visceral adiposity through activation of GR-regulated lipogenic genes, but only in the absence of MIF, which set the state of hyperinsulinemia and insulin resistance.",
journal = "Journal of Endocrinology",
title = "Mif deficiency promotes adiposity in fructose-fed mice.",
doi = "10.1530/JOE-18-0333"
}

Gligorovska, L., Bursać, B., Kovačević, S., Veličković, N., Matić, G.,& Đorđević, A.. (2019). Mif deficiency promotes adiposity in fructose-fed mice.. in Journal of Endocrinology.
https://doi.org/10.1530/JOE-18-0333

Gligorovska L, Bursać B, Kovačević S, Veličković N, Matić G, Đorđević A. Mif deficiency promotes adiposity in fructose-fed mice.. in Journal of Endocrinology. 2019;.
doi:10.1530/JOE-18-0333 .

Gligorovska, Ljupka, Bursać, Biljana, Kovačević, Sanja, Veličković, Nataša, Matić, Gordana, Đorđević, Ana, "Mif deficiency promotes adiposity in fructose-fed mice." in Journal of Endocrinology (2019),
https://doi.org/10.1530/JOE-18-0333 . .

TY  - CONF
AU  - Veličković, Nataša
AU  - Teofilović, Ana
AU  - Đorđević, Ana
AU  - Vojnović-Milutinović, Danijela
AU  - Bursać, Biljana
AU  - Brkljačić, Jelena
AU  - Elaković, Ivana
AU  - Kovačević, Sanja
AU  - Gligorovska, Ljupka
AU  - Radovanović, Marina
AU  - Preitner, Frederic
AU  - Tappy, Luc
AU  - Matić, Gordana
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5253
AB  - The aim: High fructose diet and chronic stress were both
linked with metabolic disturbances. Thus, we analyzed
their separate and combined effects on metabolic ho-
meostasis, with particular focus on hepatic lipogenesis
and gluconeogenesis.
Methods: Male Wistar rats were subjected to 9-week
20% fructose diet and/or 4-week chronic unpredict-
able stress. The following morphological and bio-
chemical parameters of lipid and glucose metabolism
were measured: body and liver mass, energy intake,
blood glucose and plasma insulin levels, free fatty ac-
ids (FFA), lactate, triglycerides (TG) and VLDL-TG, as
well as hepatic VLDL production rate, total hepatic TG
and palmitate and stearate percentage shares. Fur-
thermore, the expression of transcriptional regulators
and enzymes of hepatic de novo lipogenesis (DNL), li-
poprotein export and gluconeogenesis were analyzed.
Results: Although energy intake was increased after
fructose diet, body and liver mass remained unaltered.
Plasma TG were elevated in both fructose-fed groups,
whereas FFA were increased in the non-stressed fruc-
tose-fed group. Parameters of hepatic TG and VLDL
production and export were unaffected, except for the
hepatic palmitate production which was increased after
combined treatment. The increments of fractional DNL
and palmitate production accompanied the upregu-
lation of lipogenic enzymes, fatty acid sythase and
acetyl-CoA carboxylase, which was, interestingly, not
preceeded by the increase of their transcriptional reg-
ulators. In both fructose-fed groups blood glucose level
was increased, although hepatic gluconeogenesis
was unaffected.
Conclusion: Combined stress/fructose treatment is
more aggravating than separate treatments, since it
leads to an increase in hepatic de novo lipogenesis
and total hepatic TG palmitate, without concomitant
changes in VLDL production and export.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Program & Book of Abstracts: IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia.
T1  - De novo lipogenesis and gluconeogenesis in the liver of male fructose-fed rats exposed to chronic stress
SP  - 18
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5253
ER  - 

@conference{
author = "Veličković, Nataša and Teofilović, Ana and Đorđević, Ana and Vojnović-Milutinović, Danijela and Bursać, Biljana and Brkljačić, Jelena and Elaković, Ivana and Kovačević, Sanja and Gligorovska, Ljupka and Radovanović, Marina and Preitner, Frederic and Tappy, Luc and Matić, Gordana",
year = "2018",
abstract = "The aim: High fructose diet and chronic stress were both
linked with metabolic disturbances. Thus, we analyzed
their separate and combined effects on metabolic ho-
meostasis, with particular focus on hepatic lipogenesis
and gluconeogenesis.
Methods: Male Wistar rats were subjected to 9-week
20% fructose diet and/or 4-week chronic unpredict-
able stress. The following morphological and bio-
chemical parameters of lipid and glucose metabolism
were measured: body and liver mass, energy intake,
blood glucose and plasma insulin levels, free fatty ac-
ids (FFA), lactate, triglycerides (TG) and VLDL-TG, as
well as hepatic VLDL production rate, total hepatic TG
and palmitate and stearate percentage shares. Fur-
thermore, the expression of transcriptional regulators
and enzymes of hepatic de novo lipogenesis (DNL), li-
poprotein export and gluconeogenesis were analyzed.
Results: Although energy intake was increased after
fructose diet, body and liver mass remained unaltered.
Plasma TG were elevated in both fructose-fed groups,
whereas FFA were increased in the non-stressed fruc-
tose-fed group. Parameters of hepatic TG and VLDL
production and export were unaffected, except for the
hepatic palmitate production which was increased after
combined treatment. The increments of fractional DNL
and palmitate production accompanied the upregu-
lation of lipogenic enzymes, fatty acid sythase and
acetyl-CoA carboxylase, which was, interestingly, not
preceeded by the increase of their transcriptional reg-
ulators. In both fructose-fed groups blood glucose level
was increased, although hepatic gluconeogenesis
was unaffected.
Conclusion: Combined stress/fructose treatment is
more aggravating than separate treatments, since it
leads to an increase in hepatic de novo lipogenesis
and total hepatic TG palmitate, without concomitant
changes in VLDL production and export.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Program & Book of Abstracts: IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia.",
title = "De novo lipogenesis and gluconeogenesis in the liver of male fructose-fed rats exposed to chronic stress",
pages = "18",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5253"
}

Veličković, N., Teofilović, A., Đorđević, A., Vojnović-Milutinović, D., Bursać, B., Brkljačić, J., Elaković, I., Kovačević, S., Gligorovska, L., Radovanović, M., Preitner, F., Tappy, L.,& Matić, G.. (2018). De novo lipogenesis and gluconeogenesis in the liver of male fructose-fed rats exposed to chronic stress. in Program & Book of Abstracts: IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia.
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 18.
https://hdl.handle.net/21.15107/rcub_ibiss_5253

Veličković N, Teofilović A, Đorđević A, Vojnović-Milutinović D, Bursać B, Brkljačić J, Elaković I, Kovačević S, Gligorovska L, Radovanović M, Preitner F, Tappy L, Matić G. De novo lipogenesis and gluconeogenesis in the liver of male fructose-fed rats exposed to chronic stress. in Program & Book of Abstracts: IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia.. 2018;:18.
https://hdl.handle.net/21.15107/rcub_ibiss_5253 .

Veličković, Nataša, Teofilović, Ana, Đorđević, Ana, Vojnović-Milutinović, Danijela, Bursać, Biljana, Brkljačić, Jelena, Elaković, Ivana, Kovačević, Sanja, Gligorovska, Ljupka, Radovanović, Marina, Preitner, Frederic, Tappy, Luc, Matić, Gordana, "De novo lipogenesis and gluconeogenesis in the liver of male fructose-fed rats exposed to chronic stress" in Program & Book of Abstracts: IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia. (2018):18,
https://hdl.handle.net/21.15107/rcub_ibiss_5253 .

TY  - CONF
AU  - Gligorovska, Ljupka
AU  - Teofilović, Ana
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Matić, Gordana
AU  - Đorđević, Ana
PY  - 2018
UR  - https://radar.ibiss.bg.ac.rs/handle/handle/123456789/3161
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3321
AB  - Introduction: The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in the regulation of energy metabolism and glucocorticoid action in the liver. Genetic deletion of Mif may contribute to the development of systemic insulin resistance, especially in the setting of fructose overload that can be associated with perturbed hepatic metabolism. The aim: The aim of the present study was to elucidate the impact of combined effects of Mif deficiency and dietary sugar on energy metabolism and insulin sensitivity in the liver of male mice. Methods: Wild type (WT) and Mif deficient (MIF-/-) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on energy intake, and indicators of insulin sensitivity and glucocorticoid receptor (GR) signaling. Deregulation of Akt signaling pathway was used as a hallmark of hepatic insulin resistance. Changes in energy metabolism were estimated by AMP-activated protein kinase (AMPK) and SIRT1 protein levels. Results: All fructose-fed animals had increased energy intake, while elevated APMK and SIRT1 protein levels compared to the WT ones. Although enhanced glucocorticoid prereceptor metabolism was observed in all fructose-fed mice, GR protein level was increased only in MIF-/- animals. Mif deficient animals exibited impaired systemic insulin sensitivity. However, the impaired hepatic insulin signaling, revealed by decreased pAkt/total Akt ratio, was observed only in fructose-fed MIF-/- animals. Conclusion: The results showed that Mif deficiency under the conditions of dietary fructose overload leads to systemic insulin resistance, and impaired hepatic insulin signaling and energy metabolism, possibly through enhanced glucocorticoid signaling.
PB  - nstitute for Biological Research "Siniša Stanković"
T1  - Glucocorticoid-mediated effects of mif deficiency and fructose - enriched diet on energy metabolism in the mouse liver
SP  - 17
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3321
ER  - 

@conference{
author = "Gligorovska, Ljupka and Teofilović, Ana and Veličković, Nataša and Vojnović-Milutinović, Danijela and Matić, Gordana and Đorđević, Ana",
year = "2018",
abstract = "Introduction: The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in the regulation of energy metabolism and glucocorticoid action in the liver. Genetic deletion of Mif may contribute to the development of systemic insulin resistance, especially in the setting of fructose overload that can be associated with perturbed hepatic metabolism. The aim: The aim of the present study was to elucidate the impact of combined effects of Mif deficiency and dietary sugar on energy metabolism and insulin sensitivity in the liver of male mice. Methods: Wild type (WT) and Mif deficient (MIF-/-) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on energy intake, and indicators of insulin sensitivity and glucocorticoid receptor (GR) signaling. Deregulation of Akt signaling pathway was used as a hallmark of hepatic insulin resistance. Changes in energy metabolism were estimated by AMP-activated protein kinase (AMPK) and SIRT1 protein levels. Results: All fructose-fed animals had increased energy intake, while elevated APMK and SIRT1 protein levels compared to the WT ones. Although enhanced glucocorticoid prereceptor metabolism was observed in all fructose-fed mice, GR protein level was increased only in MIF-/- animals. Mif deficient animals exibited impaired systemic insulin sensitivity. However, the impaired hepatic insulin signaling, revealed by decreased pAkt/total Akt ratio, was observed only in fructose-fed MIF-/- animals. Conclusion: The results showed that Mif deficiency under the conditions of dietary fructose overload leads to systemic insulin resistance, and impaired hepatic insulin signaling and energy metabolism, possibly through enhanced glucocorticoid signaling.",
publisher = "nstitute for Biological Research "Siniša Stanković"",
title = "Glucocorticoid-mediated effects of mif deficiency and fructose - enriched diet on energy metabolism in the mouse liver",
pages = "17",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3321"
}

Gligorovska, L., Teofilović, A., Veličković, N., Vojnović-Milutinović, D., Matić, G.,& Đorđević, A.. (2018). Glucocorticoid-mediated effects of mif deficiency and fructose - enriched diet on energy metabolism in the mouse liver. 
nstitute for Biological Research "Siniša Stanković"., 17.
https://hdl.handle.net/21.15107/rcub_ibiss_3321

Gligorovska L, Teofilović A, Veličković N, Vojnović-Milutinović D, Matić G, Đorđević A. Glucocorticoid-mediated effects of mif deficiency and fructose - enriched diet on energy metabolism in the mouse liver. 2018;:17.
https://hdl.handle.net/21.15107/rcub_ibiss_3321 .

Gligorovska, Ljupka, Teofilović, Ana, Veličković, Nataša, Vojnović-Milutinović, Danijela, Matić, Gordana, Đorđević, Ana, "Glucocorticoid-mediated effects of mif deficiency and fructose - enriched diet on energy metabolism in the mouse liver" (2018):17,
https://hdl.handle.net/21.15107/rcub_ibiss_3321 .

TY  - JOUR
AU  - Bursać, Biljana
AU  - Đorđević, Ana
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Petrović, Snježana
AU  - Teofilović, Ana
AU  - Gligorovska, Ljupka
AU  - Preitner, Frederic
AU  - Tappy, Luc
AU  - Matić, Gordana
PY  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S0303720718301345?via%3Dihub
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29729371
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3060
AB  - Both fructose overconsumption and increased glucocorticoids secondary to chronic stress may contribute to overall dyslipidemia. In this study we specifically assessed the effects and interactions of dietary fructose and chronic stress on lipid metabolism in the visceral adipose tissue (VAT) of male Wistar rats. We analyzed the effects of 9-week 20% high fructose diet and 4-week chronic unpredictable stress, separately and in combination, on VAT histology, glucocorticoid prereceptor metabolism, glucocorticoid receptor subcellular redistribution and expression of major metabolic genes. Blood triglycerides and fatty acid composition were also measured to assess hepatic Δ9 desaturase activity. The results showed that fructose diet increased blood triglycerides and Δ9 desaturase activity. On the other hand, stress led to corticosterone elevation, glucocorticoid receptor activation and decrease in adipocyte size, while phosphoenolpyruvate carboxykinase, adipose tissue triglyceride lipase, FAT/CD36 and sterol regulatory element binding protein-1c (SREBP-1c) were increased, pointing to VAT lipolysis and glyceroneogenesis. The combination of stress and fructose diet was associated with marked stimulation of fatty acid synthase and acetyl-CoA carboxylase mRNA level and with increased 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase protein levels, suggesting a coordinated increase in hexose monophosphate shunt and de novo lipogenesis. It however did not influence the level of peroxisome proliferator-activated receptor-gamma, SREBP-1c and carbohydrate responsive element-binding protein. In conclusion, our results showed that only combination of dietary fructose and stress increase glucocorticoid prereceptor metabolism and stimulates lipogenic enzyme expression suggesting that interaction between stress and fructose may be instrumental in promoting VAT expansion and dysfunction.
T2  - Molecular and Cellular Endocrinology
T1  - Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet.
DO  - 10.1016/j.mce.2018.04.015
ER  - 

@article{
author = "Bursać, Biljana and Đorđević, Ana and Veličković, Nataša and Vojnović-Milutinović, Danijela and Petrović, Snježana and Teofilović, Ana and Gligorovska, Ljupka and Preitner, Frederic and Tappy, Luc and Matić, Gordana",
year = "2018",
abstract = "Both fructose overconsumption and increased glucocorticoids secondary to chronic stress may contribute to overall dyslipidemia. In this study we specifically assessed the effects and interactions of dietary fructose and chronic stress on lipid metabolism in the visceral adipose tissue (VAT) of male Wistar rats. We analyzed the effects of 9-week 20% high fructose diet and 4-week chronic unpredictable stress, separately and in combination, on VAT histology, glucocorticoid prereceptor metabolism, glucocorticoid receptor subcellular redistribution and expression of major metabolic genes. Blood triglycerides and fatty acid composition were also measured to assess hepatic Δ9 desaturase activity. The results showed that fructose diet increased blood triglycerides and Δ9 desaturase activity. On the other hand, stress led to corticosterone elevation, glucocorticoid receptor activation and decrease in adipocyte size, while phosphoenolpyruvate carboxykinase, adipose tissue triglyceride lipase, FAT/CD36 and sterol regulatory element binding protein-1c (SREBP-1c) were increased, pointing to VAT lipolysis and glyceroneogenesis. The combination of stress and fructose diet was associated with marked stimulation of fatty acid synthase and acetyl-CoA carboxylase mRNA level and with increased 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase protein levels, suggesting a coordinated increase in hexose monophosphate shunt and de novo lipogenesis. It however did not influence the level of peroxisome proliferator-activated receptor-gamma, SREBP-1c and carbohydrate responsive element-binding protein. In conclusion, our results showed that only combination of dietary fructose and stress increase glucocorticoid prereceptor metabolism and stimulates lipogenic enzyme expression suggesting that interaction between stress and fructose may be instrumental in promoting VAT expansion and dysfunction.",
journal = "Molecular and Cellular Endocrinology",
title = "Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet.",
doi = "10.1016/j.mce.2018.04.015"
}

Bursać, B., Đorđević, A., Veličković, N., Vojnović-Milutinović, D., Petrović, S., Teofilović, A., Gligorovska, L., Preitner, F., Tappy, L.,& Matić, G.. (2018). Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet.. in Molecular and Cellular Endocrinology.
https://doi.org/10.1016/j.mce.2018.04.015

Bursać B, Đorđević A, Veličković N, Vojnović-Milutinović D, Petrović S, Teofilović A, Gligorovska L, Preitner F, Tappy L, Matić G. Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet.. in Molecular and Cellular Endocrinology. 2018;.
doi:10.1016/j.mce.2018.04.015 .

Bursać, Biljana, Đorđević, Ana, Veličković, Nataša, Vojnović-Milutinović, Danijela, Petrović, Snježana, Teofilović, Ana, Gligorovska, Ljupka, Preitner, Frederic, Tappy, Luc, Matić, Gordana, "Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet." in Molecular and Cellular Endocrinology (2018),
https://doi.org/10.1016/j.mce.2018.04.015 . .

TY  - CONF
AU  - Gligorovska, Ljupka
AU  - Đorđević, Ana
AU  - Bursać, Biljana
AU  - Teofilović, Ana
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Kovačević, Sanja
AU  - Matić, Gordana
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5257
AB  - Introduction: The macrophage migration inhibitory factor (MIF) is a pro-inflammatory
cytokine involved in metabolic inflammation and regulation of glucocorticoid
action. Low-grade inflammation in adipose tissue is associated with obesity and
dyslipidemia and may be caused by fructose-enriched diet. We hypothesized that
the effects of MIF deficiency on lipid metabolism in adipose tissue, after high fructose
consumption, could be mediated by glucocorticoids (GCs) as potent regulators of
energy metabolism.
Methods: We analyzed the effects of 9-week 20% fructose-enriched diet on energy
intake, body mass, intra-abdominal adipose tissue mass and histology in MIF wild
type (WT) and MIF deficient (MIF−/−) C57Bl/6J mice. Expression of key transcriptional
regulators involved in adipogenesis and lipogenesis, peroxisome-proliferator-
activated receptor γ (PPARγ) and sterol regulatory element-binding protein-1
(SREBP-1), was also assessed. Glucocorticoid signaling was characterized by
prereceptor metabolism, glucocorticoid receptor (GR) protein level and
phosphorylation, and expression of GC-target genes involved in lipogenesis.
Results: Both WT and MIF−/− mice on fructose diet had increased energy intake, but
the elevation of adipose tissue mass and enlargement of adipocytes were observed
only in fructose-fed MIF−/− mice. Elevated GR protein level and its activating Ser220
phosphorylation, enhanced glucocorticoid prereceptor metabolism, an increase in
PPARγ and SREBP-1 levels and induced expression of all examined lipogenic genes
were also observed in MIF−/− mice on fructose diet.
Conclusion: The results show that only under fructose caloric overload MIF deficiency
results in lipogenesis and adipocyte hyperthrophy and that this effect might be
mediated by enhanced glucocorticoid signalling in intra-abdominal adipose tissue
PB  - Belgrade: University of Belgrade, Faculty of Biology
C3  - Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
T1  - Glucocorticoid-mediated effects of MIF deficiency and fructose-enriched diet on lipid metabolism in the mouse intra-abdominal adipose tissue
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5257
ER  - 

@conference{
author = "Gligorovska, Ljupka and Đorđević, Ana and Bursać, Biljana and Teofilović, Ana and Veličković, Nataša and Vojnović-Milutinović, Danijela and Kovačević, Sanja and Matić, Gordana",
year = "2017",
abstract = "Introduction: The macrophage migration inhibitory factor (MIF) is a pro-inflammatory
cytokine involved in metabolic inflammation and regulation of glucocorticoid
action. Low-grade inflammation in adipose tissue is associated with obesity and
dyslipidemia and may be caused by fructose-enriched diet. We hypothesized that
the effects of MIF deficiency on lipid metabolism in adipose tissue, after high fructose
consumption, could be mediated by glucocorticoids (GCs) as potent regulators of
energy metabolism.
Methods: We analyzed the effects of 9-week 20% fructose-enriched diet on energy
intake, body mass, intra-abdominal adipose tissue mass and histology in MIF wild
type (WT) and MIF deficient (MIF−/−) C57Bl/6J mice. Expression of key transcriptional
regulators involved in adipogenesis and lipogenesis, peroxisome-proliferator-
activated receptor γ (PPARγ) and sterol regulatory element-binding protein-1
(SREBP-1), was also assessed. Glucocorticoid signaling was characterized by
prereceptor metabolism, glucocorticoid receptor (GR) protein level and
phosphorylation, and expression of GC-target genes involved in lipogenesis.
Results: Both WT and MIF−/− mice on fructose diet had increased energy intake, but
the elevation of adipose tissue mass and enlargement of adipocytes were observed
only in fructose-fed MIF−/− mice. Elevated GR protein level and its activating Ser220
phosphorylation, enhanced glucocorticoid prereceptor metabolism, an increase in
PPARγ and SREBP-1 levels and induced expression of all examined lipogenic genes
were also observed in MIF−/− mice on fructose diet.
Conclusion: The results show that only under fructose caloric overload MIF deficiency
results in lipogenesis and adipocyte hyperthrophy and that this effect might be
mediated by enhanced glucocorticoid signalling in intra-abdominal adipose tissue",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.",
title = "Glucocorticoid-mediated effects of MIF deficiency and fructose-enriched diet on lipid metabolism in the mouse intra-abdominal adipose tissue",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5257"
}

Gligorovska, L., Đorđević, A., Bursać, B., Teofilović, A., Veličković, N., Vojnović-Milutinović, D., Kovačević, S.,& Matić, G.. (2017). Glucocorticoid-mediated effects of MIF deficiency and fructose-enriched diet on lipid metabolism in the mouse intra-abdominal adipose tissue. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
Belgrade: University of Belgrade, Faculty of Biology., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_5257

Gligorovska L, Đorđević A, Bursać B, Teofilović A, Veličković N, Vojnović-Milutinović D, Kovačević S, Matić G. Glucocorticoid-mediated effects of MIF deficiency and fructose-enriched diet on lipid metabolism in the mouse intra-abdominal adipose tissue. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.. 2017;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_5257 .

Gligorovska, Ljupka, Đorđević, Ana, Bursać, Biljana, Teofilović, Ana, Veličković, Nataša, Vojnović-Milutinović, Danijela, Kovačević, Sanja, Matić, Gordana, "Glucocorticoid-mediated effects of MIF deficiency and fructose-enriched diet on lipid metabolism in the mouse intra-abdominal adipose tissue" in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia. (2017):38,
https://hdl.handle.net/21.15107/rcub_ibiss_5257 .