TY  - CONF
AU  - Budnar Šoškić, Marta
AU  - Zakić, Tamara
AU  - Korać, Aleksandra
AU  - Korać, Bato
AU  - Janković, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6526
AB  - Тight control of the lipid-deposition function of white adipose tissue (WAT) defines the overall metabolic homeostasis and entails coordinated antioxidant response. We aimed to reveal temporal changes in the antioxidant defence (AD) that is a prerequisite for lipid metabolism in the visceral WAT over 45 days of re-acclimation to room temperature (RT, 22±1 °C) in rats pre-acclimated to cold (45 days, 4±1 °C). The Nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream antioxidant targets, as well as key lipogenic enzymes were examined in epididymal WAT (eWAT) and compared to the RT-maintained control. Upregulation of Nrf2 protein expression observed from the 1-12th day of re-acclimation was followed by an increase in the glutathione level (3-7th day) and the protein expression of copper, zinc superoxide dismutase (3-12th day), manganese superoxide dismutase (1-12th day), thioredoxin (1-45th day), and glutathione peroxidase (1-45th day). Such time-dependent changes in AD during re-acclimation coincided with increases in the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase that were further supported by elevated glyceraldehyde 3-phosphate dehydrogenase and glucose 6-phosphate dehydrogenase protein levels. Observed redox-metabolic integration in eWAT resulted in the restitution of relative eWAT mass on the 12th day of re-acclimation. It can be concluded that Nrf2-coordinated redox-metabolic changes drive the restitution of eWAT lipid depot during the re-acclimation of rats after cold. These results show a novel role of Nrf2 in regulating redox-metabolic signaling under homeostatic conditions and its relevance in visceral adiposity in different metabolic diseases.
PB  - Elsevier
C3  - Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
T1  - Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold
DO  - 10.1016/j.freeradbiomed.2023.03.183
SP  - 26
ER  - 

@conference{
author = "Budnar Šoškić, Marta and Zakić, Tamara and Korać, Aleksandra and Korać, Bato and Janković, Aleksandra",
year = "2023",
abstract = "Тight control of the lipid-deposition function of white adipose tissue (WAT) defines the overall metabolic homeostasis and entails coordinated antioxidant response. We aimed to reveal temporal changes in the antioxidant defence (AD) that is a prerequisite for lipid metabolism in the visceral WAT over 45 days of re-acclimation to room temperature (RT, 22±1 °C) in rats pre-acclimated to cold (45 days, 4±1 °C). The Nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream antioxidant targets, as well as key lipogenic enzymes were examined in epididymal WAT (eWAT) and compared to the RT-maintained control. Upregulation of Nrf2 protein expression observed from the 1-12th day of re-acclimation was followed by an increase in the glutathione level (3-7th day) and the protein expression of copper, zinc superoxide dismutase (3-12th day), manganese superoxide dismutase (1-12th day), thioredoxin (1-45th day), and glutathione peroxidase (1-45th day). Such time-dependent changes in AD during re-acclimation coincided with increases in the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase that were further supported by elevated glyceraldehyde 3-phosphate dehydrogenase and glucose 6-phosphate dehydrogenase protein levels. Observed redox-metabolic integration in eWAT resulted in the restitution of relative eWAT mass on the 12th day of re-acclimation. It can be concluded that Nrf2-coordinated redox-metabolic changes drive the restitution of eWAT lipid depot during the re-acclimation of rats after cold. These results show a novel role of Nrf2 in regulating redox-metabolic signaling under homeostatic conditions and its relevance in visceral adiposity in different metabolic diseases.",
publisher = "Elsevier",
journal = "Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria",
title = "Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold",
doi = "10.1016/j.freeradbiomed.2023.03.183",
pages = "26"
}

Budnar Šoškić, M., Zakić, T., Korać, A., Korać, B.,& Janković, A.. (2023). Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
Elsevier., 26.
https://doi.org/10.1016/j.freeradbiomed.2023.03.183

Budnar Šoškić M, Zakić T, Korać A, Korać B, Janković A. Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria. 2023;:26.
doi:10.1016/j.freeradbiomed.2023.03.183 .

Budnar Šoškić, Marta, Zakić, Tamara, Korać, Aleksandra, Korać, Bato, Janković, Aleksandra, "Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold" in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria (2023):26,
https://doi.org/10.1016/j.freeradbiomed.2023.03.183 . .

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Korać, Aleksandra
AU  - Korać, Bato
AU  - Janković, Aleksandra
PY  - 2022
UR  - https://www.mdpi.com/1999-4923/14/7/1368
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35890263
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9324995
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5071
AB  - The beneficial effects of l-arginine supplementation in obesity and type II diabetes involve white adipose tissue (WAT) reduction and increased substrate oxidation. We aimed to test the potential of l-arginine to induce WAT browning. Therefore, the molecular basis of browning was investigated in retroperitoneal WAT (rpWAT) of rats exposed to cold or treated with 2.25% l-arginine for 1, 3, and 7 days. Compared to untreated control, levels of inducible nitric oxide (NO) synthase protein expression and NO signaling increased in both cold-exposed and l-arginine-treated groups. These increases coincided with the appearance of multilocular adipocytes and increased expression levels of uncoupling protein 1 (UCP1), thermogenic and beige adipocyte-specific genes (Cidea, Cd137, and Tmem26), mitochondriogenesis markers (peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α, mitochondrial DNA copy number), nuclear respiratory factor 1, PPARα and their respective downstream lipid oxidation enzymes after l-arginine treatment. Such browning phenotype in the l-arginine-treated group was concordant with end-course decreases in leptinaemia, rpWAT mass, and body weight. In conclusion, l-arginine mimics cold-mediated increases in NO signaling in rpWAT and induces molecular and structural fingerprints of rpWAT browning. The results endorse l-arginine as a pharmaceutical alternative to cold exposure, which could be of great interest in obesity and associated metabolic diseases.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold.
IS  - 7
VL  - 14
DO  - 10.3390/pharmaceutics14071368
SP  - 1368
ER  - 

@article{
author = "Kalezić, Anđelika and Korać, Aleksandra and Korać, Bato and Janković, Aleksandra",
year = "2022",
abstract = "The beneficial effects of l-arginine supplementation in obesity and type II diabetes involve white adipose tissue (WAT) reduction and increased substrate oxidation. We aimed to test the potential of l-arginine to induce WAT browning. Therefore, the molecular basis of browning was investigated in retroperitoneal WAT (rpWAT) of rats exposed to cold or treated with 2.25% l-arginine for 1, 3, and 7 days. Compared to untreated control, levels of inducible nitric oxide (NO) synthase protein expression and NO signaling increased in both cold-exposed and l-arginine-treated groups. These increases coincided with the appearance of multilocular adipocytes and increased expression levels of uncoupling protein 1 (UCP1), thermogenic and beige adipocyte-specific genes (Cidea, Cd137, and Tmem26), mitochondriogenesis markers (peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α, mitochondrial DNA copy number), nuclear respiratory factor 1, PPARα and their respective downstream lipid oxidation enzymes after l-arginine treatment. Such browning phenotype in the l-arginine-treated group was concordant with end-course decreases in leptinaemia, rpWAT mass, and body weight. In conclusion, l-arginine mimics cold-mediated increases in NO signaling in rpWAT and induces molecular and structural fingerprints of rpWAT browning. The results endorse l-arginine as a pharmaceutical alternative to cold exposure, which could be of great interest in obesity and associated metabolic diseases.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold.",
number = "7",
volume = "14",
doi = "10.3390/pharmaceutics14071368",
pages = "1368"
}

Kalezić, A., Korać, A., Korać, B.,& Janković, A.. (2022). l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold.. in Pharmaceutics
Basel: MDPI., 14(7), 1368.
https://doi.org/10.3390/pharmaceutics14071368

Kalezić A, Korać A, Korać B, Janković A. l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold.. in Pharmaceutics. 2022;14(7):1368.
doi:10.3390/pharmaceutics14071368 .

Kalezić, Anđelika, Korać, Aleksandra, Korać, Bato, Janković, Aleksandra, "l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold." in Pharmaceutics, 14, no. 7 (2022):1368,
https://doi.org/10.3390/pharmaceutics14071368 . .

TY  - CONF
AU  - Janković, Aleksandra
AU  - Kalezić, Anđelika
AU  - Zakić, Tamara
AU  - Budnar Šoškić, Marta
AU  - Korać, Aleksandra
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5127
AB  - Uncoupling protein 1 (UCP1) is a molecular hallmark of thermogenic adipocytes. It can also reside in the unilocular adipocytes of white adipose tissue (WAT) that do not possess almost any oxidation and thermogenesis capacity. Therefore, the significance of UCP1 in WAT is vague. To clarify the physiological role of UCP1 in white adipocytes we aimed to investigate the relation of UCP1 expression with the components of redox-adaptive homeostasis and metabolic function in WAT. Toward this, we investigated the expression pattern of UCP1 with Nrf2 and its downstream targets, glutathione (GSH), and lipid peroxidation levels during extensive lipolysis induced by long-term cold exposure and during reversal, when lipid deposits in adipocytes recover, upon re-acclimation from cold to room temperature (RT). To this end, stated molecular targets were investigated at different time points during 45 days of cold acclimation and re-acclimation in the rat retroperitoneal WAT (rpWAT) and compared to respective RT and cold-acclimated controls. The results have shown that in response to cold-induced lipid mobilization transient induction of UCP1 precedes Nrf2 expression and upregulation of downstream antioxidant enzymes (such as MnSOD and GST). The reverse sequence of molecular events was observed during the early (1-12. days) and late (12-45. days) periods of re-acclimation from cold to RT. Namely, in the initial days of re-acclimation high lipogenesis and redox threshold (GSH, and expression of CuZnSOD and MnSOD) correspond to lower UCP1 levels. From the moment of restitution of lipid reserves (revealed by rpWAT mass) and on, UCP1, GSH, and most antioxidant enzymes return to their RT control values. The results emphasize that UCP1 and Nrf2 represent levers of redox-metabolic seesaw fine-tuning of redox homeostasis for optimal regulation of lipid mobilization and deposition in white adipocytes. Research is supported by the Science Fund of the Republic of Serbia, PROMIS, #6066747-WARMED.
PB  - Society for Free Radical Research-Europe
C3  - Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
T1  - UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue
DO  - 10.1016/j.freeradbiomed.2022.06.152
SP  - 35
ER  - 

@conference{
author = "Janković, Aleksandra and Kalezić, Anđelika and Zakić, Tamara and Budnar Šoškić, Marta and Korać, Aleksandra",
year = "2022",
abstract = "Uncoupling protein 1 (UCP1) is a molecular hallmark of thermogenic adipocytes. It can also reside in the unilocular adipocytes of white adipose tissue (WAT) that do not possess almost any oxidation and thermogenesis capacity. Therefore, the significance of UCP1 in WAT is vague. To clarify the physiological role of UCP1 in white adipocytes we aimed to investigate the relation of UCP1 expression with the components of redox-adaptive homeostasis and metabolic function in WAT. Toward this, we investigated the expression pattern of UCP1 with Nrf2 and its downstream targets, glutathione (GSH), and lipid peroxidation levels during extensive lipolysis induced by long-term cold exposure and during reversal, when lipid deposits in adipocytes recover, upon re-acclimation from cold to room temperature (RT). To this end, stated molecular targets were investigated at different time points during 45 days of cold acclimation and re-acclimation in the rat retroperitoneal WAT (rpWAT) and compared to respective RT and cold-acclimated controls. The results have shown that in response to cold-induced lipid mobilization transient induction of UCP1 precedes Nrf2 expression and upregulation of downstream antioxidant enzymes (such as MnSOD and GST). The reverse sequence of molecular events was observed during the early (1-12. days) and late (12-45. days) periods of re-acclimation from cold to RT. Namely, in the initial days of re-acclimation high lipogenesis and redox threshold (GSH, and expression of CuZnSOD and MnSOD) correspond to lower UCP1 levels. From the moment of restitution of lipid reserves (revealed by rpWAT mass) and on, UCP1, GSH, and most antioxidant enzymes return to their RT control values. The results emphasize that UCP1 and Nrf2 represent levers of redox-metabolic seesaw fine-tuning of redox homeostasis for optimal regulation of lipid mobilization and deposition in white adipocytes. Research is supported by the Science Fund of the Republic of Serbia, PROMIS, #6066747-WARMED.",
publisher = "Society for Free Radical Research-Europe",
journal = "Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium",
title = "UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue",
doi = "10.1016/j.freeradbiomed.2022.06.152",
pages = "35"
}

Janković, A., Kalezić, A., Zakić, T., Budnar Šoškić, M.,& Korać, A.. (2022). UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
Society for Free Radical Research-Europe., 35.
https://doi.org/10.1016/j.freeradbiomed.2022.06.152

Janković A, Kalezić A, Zakić T, Budnar Šoškić M, Korać A. UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. 2022;:35.
doi:10.1016/j.freeradbiomed.2022.06.152 .

Janković, Aleksandra, Kalezić, Anđelika, Zakić, Tamara, Budnar Šoškić, Marta, Korać, Aleksandra, "UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue" in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium (2022):35,
https://doi.org/10.1016/j.freeradbiomed.2022.06.152 . .

TY  - JOUR
AU  - Korać, Bato
AU  - Kalezić, Anđelika
AU  - Peković-Vaughan, Vanja
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S2213231721000355
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33579666
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4152
AB  - "Life is an instantaneous encounter of circulating matter and flowing energy" (Jean Giaja, Serbian physiologist), is one of the most elegant definitions not only of life but the relationship of redox biology and metabolism. Their evolutionary liaison has created inseparable yet dynamic homeostasis in health, which, when disrupted, leads to disease. This interconnection is even more pertinent today, in an era of increasing metabolic diseases of epidemic proportions such as obesity, metabolic syndrome, and diabetes. Despite great advances in understanding the molecular mechanisms of redox and metabolic regulation, we face significant challenges in preventing, diagnosing, and treating metabolic diseases. The etiological association and temporal overlap of these syndromes present significant challenges for the discrimination of appropriate clinical biomarkers for diagnosis, treatment, and outcome prediction. These multifactorial, multiorgan metabolic syndromes with complex etiopathogenic mechanisms are accompanied by disturbed redox equilibrium in target tissues and circulation. Free radicals and reactive species are considered both a causal factor and a consequence of disease status. Thus, determining the subtypes and levels of free radicals and reactive species, oxidatively damaged biomolecules (lipids, proteins, and nucleic acids) and antioxidant defense components as well as redox-sensitive transcription factors and fluxes of redox-dependent metabolic pathways will help define existing and establish novel redox biomarkers for stratifying metabolic diseases. This review aims to discuss diverse redox/metabolic aspects in obesity, metabolic syndrome, and diabetes, with the imperative to help establish a platform for emerging and future redox-metabolic biomarkers research in precision medicine. Future research warrants detailed investigations into the status of redox biomarkers in healthy subjects and patients, including the use of emerging 'omic' profiling technologies (e.g., redox proteomes, lipidomes, metabolomes, and transcriptomes), taking into account the influence of lifestyle (diet, physical activity, sleep, work patterns) as well as circadian ~24h fluctuations in circulatory factors and metabolites.
PB  - Elsevier BV
T2  - Redox Biology
T1  - Redox changes in obesity, metabolic syndrome, and diabetes.
DO  - 10.1016/j.redox.2021.101887
SP  - 101887
ER  - 

@article{
author = "Korać, Bato and Kalezić, Anđelika and Peković-Vaughan, Vanja and Korać, Aleksandra and Janković, Aleksandra",
year = "2021",
abstract = ""Life is an instantaneous encounter of circulating matter and flowing energy" (Jean Giaja, Serbian physiologist), is one of the most elegant definitions not only of life but the relationship of redox biology and metabolism. Their evolutionary liaison has created inseparable yet dynamic homeostasis in health, which, when disrupted, leads to disease. This interconnection is even more pertinent today, in an era of increasing metabolic diseases of epidemic proportions such as obesity, metabolic syndrome, and diabetes. Despite great advances in understanding the molecular mechanisms of redox and metabolic regulation, we face significant challenges in preventing, diagnosing, and treating metabolic diseases. The etiological association and temporal overlap of these syndromes present significant challenges for the discrimination of appropriate clinical biomarkers for diagnosis, treatment, and outcome prediction. These multifactorial, multiorgan metabolic syndromes with complex etiopathogenic mechanisms are accompanied by disturbed redox equilibrium in target tissues and circulation. Free radicals and reactive species are considered both a causal factor and a consequence of disease status. Thus, determining the subtypes and levels of free radicals and reactive species, oxidatively damaged biomolecules (lipids, proteins, and nucleic acids) and antioxidant defense components as well as redox-sensitive transcription factors and fluxes of redox-dependent metabolic pathways will help define existing and establish novel redox biomarkers for stratifying metabolic diseases. This review aims to discuss diverse redox/metabolic aspects in obesity, metabolic syndrome, and diabetes, with the imperative to help establish a platform for emerging and future redox-metabolic biomarkers research in precision medicine. Future research warrants detailed investigations into the status of redox biomarkers in healthy subjects and patients, including the use of emerging 'omic' profiling technologies (e.g., redox proteomes, lipidomes, metabolomes, and transcriptomes), taking into account the influence of lifestyle (diet, physical activity, sleep, work patterns) as well as circadian ~24h fluctuations in circulatory factors and metabolites.",
publisher = "Elsevier BV",
journal = "Redox Biology",
title = "Redox changes in obesity, metabolic syndrome, and diabetes.",
doi = "10.1016/j.redox.2021.101887",
pages = "101887"
}

Korać, B., Kalezić, A., Peković-Vaughan, V., Korać, A.,& Janković, A.. (2021). Redox changes in obesity, metabolic syndrome, and diabetes.. in Redox Biology
Elsevier BV., 101887.
https://doi.org/10.1016/j.redox.2021.101887

Korać B, Kalezić A, Peković-Vaughan V, Korać A, Janković A. Redox changes in obesity, metabolic syndrome, and diabetes.. in Redox Biology. 2021;:101887.
doi:10.1016/j.redox.2021.101887 .

Korać, Bato, Kalezić, Anđelika, Peković-Vaughan, Vanja, Korać, Aleksandra, Janković, Aleksandra, "Redox changes in obesity, metabolic syndrome, and diabetes." in Redox Biology (2021):101887,
https://doi.org/10.1016/j.redox.2021.101887 . .

TY  - JOUR
AU  - Aleksić, Marija
AU  - Kalezić, Anđelika
AU  - Saso, Luciano
AU  - Janković, Aleksandra
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4216
AB  - Brown adipose tissue (BAT) is important for maintaining whole-body metabolic and energy homeostasis. However, the effects of hypothyroidism, one of the most common diseases worldwide, which increases the risk of several metabolic disorders, on BAT redox and metabolic homeostasis remain mostly unknown. We aimed to investigate the dynamics of protein expression, enzyme activity, and localization of antioxidant defense (AD) enzymes in rat interscapular BAT upon induction of hypothyroidism by antithyroid drug methimazole for 7, 15, and 21 days. Our results showed an increased protein expression of CuZn-and Mn-superoxide dismutase, catalase, glutamyl– cysteine ligase, thioredoxin, total glutathione content, and activity of catalase and thioredoxin reductase in hypothyroid rats, compared to euthyroid control. Concomitant with the increase in AD, newly established nuclear, mitochondrial, and peroxisomal localization of AD enzymes was found. Hypothyroidism also potentiated associations between mitochondria, peroxisomes, and lipid bodies, creating specific structural–functional units. Moreover, hypothyroidism induced protein expression and nuclear translocation of a master regulator of redox-metabolic homeostasis, nuclear factor erythroid 2-related factor 2 (Nrf2), and an increased amount of 4-hydroxynonenal (4-HNE) protein adducts. The results indicate that spatiotemporal overlap in the remodeling of AD is orchestrated by Nrf2, implicating the role of 4-HNE in this process and suggesting the potential mechanism of redox-structural remodeling during BAT adaptation in hypothyroidism.
PB  - MDPI AG
T2  - Antioxidants
T1  - The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism
IS  - 4
VL  - 10
DO  - 10.3390/antiox10040591
SP  - 591
ER  - 

@article{
author = "Aleksić, Marija and Kalezić, Anđelika and Saso, Luciano and Janković, Aleksandra and Korać, Bato and Korać, Aleksandra",
year = "2021",
abstract = "Brown adipose tissue (BAT) is important for maintaining whole-body metabolic and energy homeostasis. However, the effects of hypothyroidism, one of the most common diseases worldwide, which increases the risk of several metabolic disorders, on BAT redox and metabolic homeostasis remain mostly unknown. We aimed to investigate the dynamics of protein expression, enzyme activity, and localization of antioxidant defense (AD) enzymes in rat interscapular BAT upon induction of hypothyroidism by antithyroid drug methimazole for 7, 15, and 21 days. Our results showed an increased protein expression of CuZn-and Mn-superoxide dismutase, catalase, glutamyl– cysteine ligase, thioredoxin, total glutathione content, and activity of catalase and thioredoxin reductase in hypothyroid rats, compared to euthyroid control. Concomitant with the increase in AD, newly established nuclear, mitochondrial, and peroxisomal localization of AD enzymes was found. Hypothyroidism also potentiated associations between mitochondria, peroxisomes, and lipid bodies, creating specific structural–functional units. Moreover, hypothyroidism induced protein expression and nuclear translocation of a master regulator of redox-metabolic homeostasis, nuclear factor erythroid 2-related factor 2 (Nrf2), and an increased amount of 4-hydroxynonenal (4-HNE) protein adducts. The results indicate that spatiotemporal overlap in the remodeling of AD is orchestrated by Nrf2, implicating the role of 4-HNE in this process and suggesting the potential mechanism of redox-structural remodeling during BAT adaptation in hypothyroidism.",
publisher = "MDPI AG",
journal = "Antioxidants",
title = "The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism",
number = "4",
volume = "10",
doi = "10.3390/antiox10040591",
pages = "591"
}

Aleksić, M., Kalezić, A., Saso, L., Janković, A., Korać, B.,& Korać, A.. (2021). The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism. in Antioxidants
MDPI AG., 10(4), 591.
https://doi.org/10.3390/antiox10040591

Aleksić M, Kalezić A, Saso L, Janković A, Korać B, Korać A. The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism. in Antioxidants. 2021;10(4):591.
doi:10.3390/antiox10040591 .

Aleksić, Marija, Kalezić, Anđelika, Saso, Luciano, Janković, Aleksandra, Korać, Bato, Korać, Aleksandra, "The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism" in Antioxidants, 10, no. 4 (2021):591,
https://doi.org/10.3390/antiox10040591 . .

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Aleksić, Marija
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - https://www.mdpi.com/2072-6694/13/11/2731
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4407
AB  - Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5′-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1—PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase—G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue.
T2  - Cancers
T1  - Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis
IS  - 11
VL  - 13
DO  - 10.3390/cancers13112731
SP  - 2731
ER  - 

@article{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Aleksić, Marija and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5′-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1—PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase—G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue.",
journal = "Cancers",
title = "Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis",
number = "11",
volume = "13",
doi = "10.3390/cancers13112731",
pages = "2731"
}

Kalezić, A., Udički, M., Srdić Galić, B., Aleksić, M., Korać, A., Janković, A.,& Korać, B.. (2021). Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis. in Cancers, 13(11), 2731.
https://doi.org/10.3390/cancers13112731

Kalezić A, Udički M, Srdić Galić B, Aleksić M, Korać A, Janković A, Korać B. Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis. in Cancers. 2021;13(11):2731.
doi:10.3390/cancers13112731 .

Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Aleksić, Marija, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis" in Cancers, 13, no. 11 (2021):2731,
https://doi.org/10.3390/cancers13112731 . .

TY  - JOUR
AU  - Aleksić, Marija
AU  - Golić, Igor
AU  - Kalezić, Anđelika
AU  - Janković, Aleksandra
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2021
UR  - https://www.mdpi.com/2073-4409/10/9/2248
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8472630
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4491
AB  - Despite peroxisomes being important partners of mitochondria by carrying out fatty acid oxidation in brown adipocytes, no clear evidence concerning peroxisome origin and way(s) of biogenesis exists. Herein we used methimazole-induced hypothyroidism for 7, 15, and 21 days to study peroxisomal remodeling and origin in rat brown adipocytes. We found that peroxisomes originated via both canonic, and de novo pathways. Each pathway operates in euthyroid control and over the course of hypothyroidism, in a time-dependent manner. Hypothyroidism increased the peroxisomal number by 1.8-, 3.6- and 5.8-fold on days 7, 15, and 21. Peroxisomal presence, their distribution, and their degree of maturation were heterogeneous in brown adipocytes in a Harlequin-like manner, reflecting differences in their origin. The canonic pathway, through numerous dumbbell-like and "pearls on strings" structures, supported by high levels of Pex11β and Drp1, prevailed on day 7. The de novo pathway of peroxisomal biogenesis started on day 15 and became dominant by day 21. The transition of peroxisomal biogenesis from canonic to the de novo pathway was driven by increased levels of Pex19, PMP70, Pex5S, and Pex26 and characterized by numerous tubular structures. Furthermore, specific peroxisomal origin from mitochondria, regardless of thyroid status, indicates their mutual regulation in rat brown adipocytes.
PB  - Basel: MDPI
T2  - Cells
T1  - Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner.
IS  - 9
VL  - 10
DO  - 10.3390/cells10092248
SP  - 2248
ER  - 

@article{
author = "Aleksić, Marija and Golić, Igor and Kalezić, Anđelika and Janković, Aleksandra and Korać, Bato and Korać, Aleksandra",
year = "2021",
abstract = "Despite peroxisomes being important partners of mitochondria by carrying out fatty acid oxidation in brown adipocytes, no clear evidence concerning peroxisome origin and way(s) of biogenesis exists. Herein we used methimazole-induced hypothyroidism for 7, 15, and 21 days to study peroxisomal remodeling and origin in rat brown adipocytes. We found that peroxisomes originated via both canonic, and de novo pathways. Each pathway operates in euthyroid control and over the course of hypothyroidism, in a time-dependent manner. Hypothyroidism increased the peroxisomal number by 1.8-, 3.6- and 5.8-fold on days 7, 15, and 21. Peroxisomal presence, their distribution, and their degree of maturation were heterogeneous in brown adipocytes in a Harlequin-like manner, reflecting differences in their origin. The canonic pathway, through numerous dumbbell-like and "pearls on strings" structures, supported by high levels of Pex11β and Drp1, prevailed on day 7. The de novo pathway of peroxisomal biogenesis started on day 15 and became dominant by day 21. The transition of peroxisomal biogenesis from canonic to the de novo pathway was driven by increased levels of Pex19, PMP70, Pex5S, and Pex26 and characterized by numerous tubular structures. Furthermore, specific peroxisomal origin from mitochondria, regardless of thyroid status, indicates their mutual regulation in rat brown adipocytes.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner.",
number = "9",
volume = "10",
doi = "10.3390/cells10092248",
pages = "2248"
}

Aleksić, M., Golić, I., Kalezić, A., Janković, A., Korać, B.,& Korać, A.. (2021). Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner.. in Cells
Basel: MDPI., 10(9), 2248.
https://doi.org/10.3390/cells10092248

Aleksić M, Golić I, Kalezić A, Janković A, Korać B, Korać A. Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner.. in Cells. 2021;10(9):2248.
doi:10.3390/cells10092248 .

Aleksić, Marija, Golić, Igor, Kalezić, Anđelika, Janković, Aleksandra, Korać, Bato, Korać, Aleksandra, "Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner." in Cells, 10, no. 9 (2021):2248,
https://doi.org/10.3390/cells10092248 . .

TY  - CONF
AU  - Janković, Aleksandra
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4802
AB  - Understanding mechanisms that enable/restrict the metabolic plasticity of adipose tissue (AT) is crucial for reducing the global burden of obesity and metabolic diseases. We consistently showed that metabolic reprogramming of adipose tissue is inevitably tied to redox reprogramming in numerous physiological (cold re-acclimation, hibernation) and pathophysiological states (obesity, metabolic syndrome, diabetes, cancer). Cumulative evidence suggests that AT's redox-metabolic regulatory feedback loop is under pressure in overnutrition states. Namely, an increase in glucose and fatty acid flux via adipocytes shifts the balance of redox systems (NAD(P)+/NAD(P)H, thiol - S-/SH and glutathione - GSSG/GSH, antioxidant/prooxidant enzymes), thus increasing the levels of reactive oxygen and nitrogen species (RO(N)S). When produced in a controlled manner, RO(N)S regulate the activities of numerous proteins increasing the lipid buffering capacity. Persistent nutritional overload, however, and consequent oxidative pressure may at any moment exceed the antioxidant capacity of the adipocyte leading to irreversible damage of proteins and other biomolecules, impairing metabolic and endocrine function of AT. Understanding how the "redox milieu" limits AT capacity for lipid storage and oxidation is vital for designing treatment strategies in obesity. Our results show that investigating specific panels of redox biomarkers can clearly "mark" AT depots with disrupted lipid buffering capacity, thus identifying the risk of metabolic syndrome in obesity. Besides, our research aims to target the AT contribution to metabolic diseases such as diabetes, atherosclerosis, and cancer by shifting the AT redox homeostasis. We showed that setting the "catabolic redox milieu" in AT by targeting nitric oxide (NO) and glutathione (GSH) signaling can "ignite" AT by inducing a brown AT-like thermogenic phenotype. Such redox-based approaches (NO supplementation, GSH depletion) show great therapeutic potential as an alternative to natural stimuli such as cold exposure or adrenergic stimulation. In summary, obesity and related metabolic diseases are redox diseases of AT that could be targeted by advancing selective AT-specific redox-based approaches. Investigations partially Funded by Science Fund of the Republic of Serbia, Program for Excellent Projects of Young Researchers, grant # 6066747
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  - Redox-metabolic synergy - a backbone interface for adipocentric approach to metabolic diseases
DO  - 10.1016/j.freeradbiomed.2021.08.025
SP  - S51
EP  - S52
ER  - 

@conference{
author = "Janković, Aleksandra",
year = "2021",
abstract = "Understanding mechanisms that enable/restrict the metabolic plasticity of adipose tissue (AT) is crucial for reducing the global burden of obesity and metabolic diseases. We consistently showed that metabolic reprogramming of adipose tissue is inevitably tied to redox reprogramming in numerous physiological (cold re-acclimation, hibernation) and pathophysiological states (obesity, metabolic syndrome, diabetes, cancer). Cumulative evidence suggests that AT's redox-metabolic regulatory feedback loop is under pressure in overnutrition states. Namely, an increase in glucose and fatty acid flux via adipocytes shifts the balance of redox systems (NAD(P)+/NAD(P)H, thiol - S-/SH and glutathione - GSSG/GSH, antioxidant/prooxidant enzymes), thus increasing the levels of reactive oxygen and nitrogen species (RO(N)S). When produced in a controlled manner, RO(N)S regulate the activities of numerous proteins increasing the lipid buffering capacity. Persistent nutritional overload, however, and consequent oxidative pressure may at any moment exceed the antioxidant capacity of the adipocyte leading to irreversible damage of proteins and other biomolecules, impairing metabolic and endocrine function of AT. Understanding how the "redox milieu" limits AT capacity for lipid storage and oxidation is vital for designing treatment strategies in obesity. Our results show that investigating specific panels of redox biomarkers can clearly "mark" AT depots with disrupted lipid buffering capacity, thus identifying the risk of metabolic syndrome in obesity. Besides, our research aims to target the AT contribution to metabolic diseases such as diabetes, atherosclerosis, and cancer by shifting the AT redox homeostasis. We showed that setting the "catabolic redox milieu" in AT by targeting nitric oxide (NO) and glutathione (GSH) signaling can "ignite" AT by inducing a brown AT-like thermogenic phenotype. Such redox-based approaches (NO supplementation, GSH depletion) show great therapeutic potential as an alternative to natural stimuli such as cold exposure or adrenergic stimulation. In summary, obesity and related metabolic diseases are redox diseases of AT that could be targeted by advancing selective AT-specific redox-based approaches. Investigations partially Funded by Science Fund of the Republic of Serbia, Program for Excellent Projects of Young Researchers, grant # 6066747",
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 = "Redox-metabolic synergy - a backbone interface for adipocentric approach to metabolic diseases",
doi = "10.1016/j.freeradbiomed.2021.08.025",
pages = "S51-S52"
}

Janković, A.. (2021). Redox-metabolic synergy - a backbone interface for adipocentric approach to metabolic diseases. 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.., S51-S52.
https://doi.org/10.1016/j.freeradbiomed.2021.08.025

Janković A. Redox-metabolic synergy - a backbone interface for adipocentric approach to metabolic diseases. 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;:S51-S52.
doi:10.1016/j.freeradbiomed.2021.08.025 .

Janković, Aleksandra, "Redox-metabolic synergy - a backbone interface for adipocentric approach to metabolic diseases" 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):S51-S52,
https://doi.org/10.1016/j.freeradbiomed.2021.08.025 . .