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  - 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  - JOUR
AU  - Teofilović, Ana
AU  - Vratarić, Miloš
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Mladenović, Aleksandra
AU  - Prvulović, Milica
AU  - Đorđević, Ana
PY  - 2022
UR  - https://www.frontiersin.org/articles/10.3389/fnut.2022.899255/full
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9168317
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5004
AB  - Aging is a progressive process that could disturb metabolic homeostasis in the liver via ectopic lipid accumulation, oxidative stress, and deterioration of inflammatory response. Although calorie restriction (CR) is recognized as beneficial for life span and health span prolongation, it is still unclear how late-onset CR, characterized by late beginning and short duration, affects age-related processes. The aim of this study was to examine how late-onset CR-induced metabolic adjustments impact lipid status and inflammation in the liver of old rats. The experiments were conducted on aging male Wistar rats fed ad libitum (AL) or exposed to late-onset CR (60% of AL daily intake) from 21st to 24th month. The results showed that late-onset CR reduces body weight, visceral adipose tissue and liver mass, and triglyceride levels when compared to old animals on AL diet. The ameliorating effects of CR on lipid metabolism include increased activity of AMP-activated protein kinase, suppressed de novo fatty acid synthesis, stimulated β-oxidation, decreased lipotoxicity, and limited triglyceride synthesis and packaging in the liver. Restricted diet regime, however, does not improve expression of antioxidant enzymes, although it leads to progression of age-related inflammation in the liver, partially through lower corticosterone concentration and decreased activation of glucocorticoid receptor. In conclusion, late-onset CR is able to restore age-related imbalance of lipid metabolism in the liver, but has a negative impact on hepatic inflammatory status, implying that the type of diet for older individuals must be balanced and chosen carefully with appropriate duration and start point.
T2  - Frontiers in Nutrition
T1  - Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats.
VL  - 9
DO  - 10.3389/fnut.2022.899255
SP  - 899255
ER  - 

@article{
author = "Teofilović, Ana and Vratarić, Miloš and Veličković, Nataša and Vojnović-Milutinović, Danijela and Mladenović, Aleksandra and Prvulović, Milica and Đorđević, Ana",
year = "2022",
abstract = "Aging is a progressive process that could disturb metabolic homeostasis in the liver via ectopic lipid accumulation, oxidative stress, and deterioration of inflammatory response. Although calorie restriction (CR) is recognized as beneficial for life span and health span prolongation, it is still unclear how late-onset CR, characterized by late beginning and short duration, affects age-related processes. The aim of this study was to examine how late-onset CR-induced metabolic adjustments impact lipid status and inflammation in the liver of old rats. The experiments were conducted on aging male Wistar rats fed ad libitum (AL) or exposed to late-onset CR (60% of AL daily intake) from 21st to 24th month. The results showed that late-onset CR reduces body weight, visceral adipose tissue and liver mass, and triglyceride levels when compared to old animals on AL diet. The ameliorating effects of CR on lipid metabolism include increased activity of AMP-activated protein kinase, suppressed de novo fatty acid synthesis, stimulated β-oxidation, decreased lipotoxicity, and limited triglyceride synthesis and packaging in the liver. Restricted diet regime, however, does not improve expression of antioxidant enzymes, although it leads to progression of age-related inflammation in the liver, partially through lower corticosterone concentration and decreased activation of glucocorticoid receptor. In conclusion, late-onset CR is able to restore age-related imbalance of lipid metabolism in the liver, but has a negative impact on hepatic inflammatory status, implying that the type of diet for older individuals must be balanced and chosen carefully with appropriate duration and start point.",
journal = "Frontiers in Nutrition",
title = "Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats.",
volume = "9",
doi = "10.3389/fnut.2022.899255",
pages = "899255"
}

Teofilović, A., Vratarić, M., Veličković, N., Vojnović-Milutinović, D., Mladenović, A., Prvulović, M.,& Đorđević, A.. (2022). Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats.. in Frontiers in Nutrition, 9, 899255.
https://doi.org/10.3389/fnut.2022.899255

Teofilović A, Vratarić M, Veličković N, Vojnović-Milutinović D, Mladenović A, Prvulović M, Đorđević A. Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats.. in Frontiers in Nutrition. 2022;9:899255.
doi:10.3389/fnut.2022.899255 .

Teofilović, Ana, Vratarić, Miloš, Veličković, Nataša, Vojnović-Milutinović, Danijela, Mladenović, Aleksandra, Prvulović, Milica, Đorđević, Ana, "Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats." in Frontiers in Nutrition, 9 (2022):899255,
https://doi.org/10.3389/fnut.2022.899255 . .

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  - 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  - CONF
AU  - Teofilović, Ana
AU  - Vratarić, Miloš
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
AU  - Đorđević, Ana
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4281
AB  - Objectives: Dietary restriction (DR) is the approach often used
to delay the development of age-related disorders. One of the unresolved
questions is how late beginning and short duration of DR
affects disturbed metabolic balance caused by ageing. Glucocorticoid
hormones have significant role in the regulation of energy metabolism
and inflammation, especially during ageing when their
systemic
concentration arise. The aim of this study was to examine
the impact of glucocorticoid signaling alterations induced by the
late-onset DR on metabolic inflammation in the liver of old Wistar
rats.
Methods: The experiments were conducted on 6- and
24‑month‑old male Wistar rats on ad libitum diet and
24‑month‑old animals on restrictive diet (60% of ad libitum daily
intake) from 21st to 24th month (late-onset DR). The gene expression
of proinflammatory cytokines was measured by qPCR, while
protein levels of nuclear factor κB (NFκB) and antioxidant enzymes
were determined by Western blot. Glucocorticoid signaling was
analyzed at the level of glucocorticoid prereceptor metabolism and
subcellular distribution of glucocorticoid receptor (GR). Liver corticosterone
concentration was measured by ELISA.
Results: Decreased levels of antioxidant enzymes observed
during ageing were accompanied with augmented inflammation,
characterized by increased nuclear NFκB protein level and higher
expression of Toll like receptor 4 and TNFα. Corticosterone concentration
in the liver of old rats was increased despite unchanged
level of proteins involved in glucocorticoid prereceptor metabolism.
Late-onset DR reduced adipose tissue and liver mass of old
animals, and further stimulated inflammation in the liver.
Decreased level of hepatic corticosterone after DR was a consequence
of increased expression of 5α-reductase which was in
agreement with the decreased GR protein level in the nuclear
fraction.
Conclusion: Late-onset DR did not improve expression of antioxidant
enzymes and led to progression of age-related inflammation
in the liver. This was accompanied with decreased levels of
corticosterone and GR in the nucleus implying that late-onset DR
aggravates inflammatory response through decreased glucocorticoid
signaling in the liver of old rats.
PB  - Basel: S Karger AG
C3  - Proceedings from the 4th European Summer School on Nutrigenomics; 2021 Jun 21-25; Online
T1  - Glucocorticoid Signaling Alterations Induced by Late-Onset Dietary Resctriction Aggravate Metabolic Inflammation in the Liver of Old Wistar Rats
DO  - https://doi.org/10.1159/000517609
SP  - 13
ER  - 

@conference{
author = "Teofilović, Ana and Vratarić, Miloš and Veličković, Nataša and Vojnović-Milutinović, Danijela and Prvulović, Milica and Todorović, Smilja and Mladenović, Aleksandra and Đorđević, Ana",
year = "2021",
abstract = "Objectives: Dietary restriction (DR) is the approach often used
to delay the development of age-related disorders. One of the unresolved
questions is how late beginning and short duration of DR
affects disturbed metabolic balance caused by ageing. Glucocorticoid
hormones have significant role in the regulation of energy metabolism
and inflammation, especially during ageing when their
systemic
concentration arise. The aim of this study was to examine
the impact of glucocorticoid signaling alterations induced by the
late-onset DR on metabolic inflammation in the liver of old Wistar
rats.
Methods: The experiments were conducted on 6- and
24‑month‑old male Wistar rats on ad libitum diet and
24‑month‑old animals on restrictive diet (60% of ad libitum daily
intake) from 21st to 24th month (late-onset DR). The gene expression
of proinflammatory cytokines was measured by qPCR, while
protein levels of nuclear factor κB (NFκB) and antioxidant enzymes
were determined by Western blot. Glucocorticoid signaling was
analyzed at the level of glucocorticoid prereceptor metabolism and
subcellular distribution of glucocorticoid receptor (GR). Liver corticosterone
concentration was measured by ELISA.
Results: Decreased levels of antioxidant enzymes observed
during ageing were accompanied with augmented inflammation,
characterized by increased nuclear NFκB protein level and higher
expression of Toll like receptor 4 and TNFα. Corticosterone concentration
in the liver of old rats was increased despite unchanged
level of proteins involved in glucocorticoid prereceptor metabolism.
Late-onset DR reduced adipose tissue and liver mass of old
animals, and further stimulated inflammation in the liver.
Decreased level of hepatic corticosterone after DR was a consequence
of increased expression of 5α-reductase which was in
agreement with the decreased GR protein level in the nuclear
fraction.
Conclusion: Late-onset DR did not improve expression of antioxidant
enzymes and led to progression of age-related inflammation
in the liver. This was accompanied with decreased levels of
corticosterone and GR in the nucleus implying that late-onset DR
aggravates inflammatory response through decreased glucocorticoid
signaling in the liver of old rats.",
publisher = "Basel: S Karger AG",
journal = "Proceedings from the 4th European Summer School on Nutrigenomics; 2021 Jun 21-25; Online",
title = "Glucocorticoid Signaling Alterations Induced by Late-Onset Dietary Resctriction Aggravate Metabolic Inflammation in the Liver of Old Wistar Rats",
doi = "https://doi.org/10.1159/000517609",
pages = "13"
}

Teofilović, A., Vratarić, M., Veličković, N., Vojnović-Milutinović, D., Prvulović, M., Todorović, S., Mladenović, A.,& Đorđević, A.. (2021). Glucocorticoid Signaling Alterations Induced by Late-Onset Dietary Resctriction Aggravate Metabolic Inflammation in the Liver of Old Wistar Rats. in Proceedings from the 4th European Summer School on Nutrigenomics; 2021 Jun 21-25; Online
Basel: S Karger AG., 13.
https://doi.org/https://doi.org/10.1159/000517609

Teofilović A, Vratarić M, Veličković N, Vojnović-Milutinović D, Prvulović M, Todorović S, Mladenović A, Đorđević A. Glucocorticoid Signaling Alterations Induced by Late-Onset Dietary Resctriction Aggravate Metabolic Inflammation in the Liver of Old Wistar Rats. in Proceedings from the 4th European Summer School on Nutrigenomics; 2021 Jun 21-25; Online. 2021;:13.
doi:https://doi.org/10.1159/000517609 .

Teofilović, Ana, Vratarić, Miloš, Veličković, Nataša, Vojnović-Milutinović, Danijela, Prvulović, Milica, Todorović, Smilja, Mladenović, Aleksandra, Đorđević, Ana, "Glucocorticoid Signaling Alterations Induced by Late-Onset Dietary Resctriction Aggravate Metabolic Inflammation in the Liver of Old Wistar Rats" in Proceedings from the 4th European Summer School on Nutrigenomics; 2021 Jun 21-25; Online (2021):13,
https://doi.org/https://doi.org/10.1159/000517609 . .