TY  - CONF
AU  - Zakić, Tamara
AU  - Budnar-Šoškić, Marta
AU  - Stojanović, Sara
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković-Vaughan, Vanja
AU  - Korać, Bato
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6527
AB  - The precise regulatory mechanisms of interscapular brown adipose tissue (IBAT) thermogenesis are not fully elucidated, especially those in relation to Nuclear factor erythroid 2–related factor 2 (Nrf2). We have recently shown that mice lacking functional Nrf2 (Nrf2KO) at room temperature (RT) depict thermogenic IBAT activity at the structural level. However, gene and protein expression of the main IBAT thermogenic marker uncoupling protein 1 (UCP1), and other redox-metabolic functional parameters, did not align with this apparent thermogenic activation. Here, we investigated the functional activation of IBAT in wild-type (WT) and Nrf2KO mice maintained at RT (24±1°C) or after cold acclimation (45 days, 4±1°C). We performed immunogold labelling of Nrf2 and its closely related transcription factors Nrf1, Nrf3, and nuclear respiratory factor 1 (NRF1) to determine their spatial expression patterns. Next, we measured succinate-based mitochondrial respiration as an indicator of IBAT mitochondrial oxidative function and uncoupling capacity. Electron microscopy confirmed that Nrf2KO mice at RT had the same ultrastructural characteristics as cold-exposed mice, indicating IBAT thermogenic activity. This was associated with increased mitochondrial immunogold reaction of the above redox-sensitive transcription factors indicating their activation in Nrf2KO mice at RT. In contrast to such activated phenotype, respirometry results showed that Nrf2KO mice at RT had no uncoupling activity compared to cold-exposed WT mice. Furthermore, similar respiratory pattern was observed in Nrf2KO mice acclimated to cold, regardless of increased UCP1 expression. These results demonstrate that despite the (ultra)structural recruitment of IBAT in Nrf2KO mice at RT and after cold acclimation, Nrf2 is essential for the full functional thermogenic activation of IBAT and the lack of functional Nrf2 could not be compensated with Nrf1, Nrf3, and NRF1.
PB  - Elsevier
C3  - Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
T1  - The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2
DO  - 10.1016/j.freeradbiomed.2023.03.109
SP  - 25
ER  - 

@conference{
author = "Zakić, Tamara and Budnar-Šoškić, Marta and Stojanović, Sara and Janković, Aleksandra and Korać, Aleksandra and Peković-Vaughan, Vanja and Korać, Bato",
year = "2023",
abstract = "The precise regulatory mechanisms of interscapular brown adipose tissue (IBAT) thermogenesis are not fully elucidated, especially those in relation to Nuclear factor erythroid 2–related factor 2 (Nrf2). We have recently shown that mice lacking functional Nrf2 (Nrf2KO) at room temperature (RT) depict thermogenic IBAT activity at the structural level. However, gene and protein expression of the main IBAT thermogenic marker uncoupling protein 1 (UCP1), and other redox-metabolic functional parameters, did not align with this apparent thermogenic activation. Here, we investigated the functional activation of IBAT in wild-type (WT) and Nrf2KO mice maintained at RT (24±1°C) or after cold acclimation (45 days, 4±1°C). We performed immunogold labelling of Nrf2 and its closely related transcription factors Nrf1, Nrf3, and nuclear respiratory factor 1 (NRF1) to determine their spatial expression patterns. Next, we measured succinate-based mitochondrial respiration as an indicator of IBAT mitochondrial oxidative function and uncoupling capacity. Electron microscopy confirmed that Nrf2KO mice at RT had the same ultrastructural characteristics as cold-exposed mice, indicating IBAT thermogenic activity. This was associated with increased mitochondrial immunogold reaction of the above redox-sensitive transcription factors indicating their activation in Nrf2KO mice at RT. In contrast to such activated phenotype, respirometry results showed that Nrf2KO mice at RT had no uncoupling activity compared to cold-exposed WT mice. Furthermore, similar respiratory pattern was observed in Nrf2KO mice acclimated to cold, regardless of increased UCP1 expression. These results demonstrate that despite the (ultra)structural recruitment of IBAT in Nrf2KO mice at RT and after cold acclimation, Nrf2 is essential for the full functional thermogenic activation of IBAT and the lack of functional Nrf2 could not be compensated with Nrf1, Nrf3, and NRF1.",
publisher = "Elsevier",
journal = "Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria",
title = "The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2",
doi = "10.1016/j.freeradbiomed.2023.03.109",
pages = "25"
}

Zakić, T., Budnar-Šoškić, M., Stojanović, S., Janković, A., Korać, A., Peković-Vaughan, V.,& Korać, B.. (2023). The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
Elsevier., 25.
https://doi.org/10.1016/j.freeradbiomed.2023.03.109

Zakić T, Budnar-Šoškić M, Stojanović S, Janković A, Korać A, Peković-Vaughan V, Korać B. The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria. 2023;:25.
doi:10.1016/j.freeradbiomed.2023.03.109 .

Zakić, Tamara, Budnar-Šoškić, Marta, Stojanović, Sara, Janković, Aleksandra, Korać, Aleksandra, Peković-Vaughan, Vanja, Korać, Bato, "The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2" in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria (2023):25,
https://doi.org/10.1016/j.freeradbiomed.2023.03.109 . .

TY  - JOUR
AU  - Zakić, Tamara
AU  - Stojanović, Sara
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković‐Vaughan, Vanja
AU  - Korać, Bato
PY  - 2022
UR  - https://onlinelibrary.wiley.com/doi/10.1002/biof.1931
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5385
AB  - Adaptive responses to environmental and physiological challenges, including exposure to low environmental temperature, require extensive structural, redox, and metabolic reprogramming. Detailed molecular mechanisms of such processes in the skin are lacking, especially the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and other closely related redox-sensitive transcription factors Nrf1, Nrf3, and nuclear respiratory factor (NRF1). To investigate the role of Nrf2, we examined redox and metabolic responses in the skin of wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2 KO) at room (RT, 24 ± 1°C) and cold (4 ± 1°C) temperature. Our results demonstrate distinct expression profiles of major enzymes involved in antioxidant defense and key metabolic and mitochondrial pathways in the skin, depending on the functional Nrf2 and/or cold stimulus. Nrf2 KO mice at RT displayed profound alterations in redox, mitochondrial and metabolic responses, generally akin to cold-induced skin responses in WT mice. Immunohistochemical analyses of skin cell compartments (keratinocytes, fibroblasts, hair follicle, and sebaceous gland) and spatial locations (nucleus and cytoplasm) revealed synergistic interactions between members of the Nrf transcription factor family as part of redox-metabolic reprogramming in WT mice upon cold acclimation. In contrast, Nrf2 KO mice at RT showed loss of NRF1 expression and a compensatory activation of Nrf1/Nrf3, which was abolished upon cold, concomitant with blunted redox-metabolic responses. These data show for the first time a novel role for Nrf2 in skin physiology in response to low environmental temperature, with important implications in human connective tissue diseases with altered thermogenic responses.
T2  - BioFactors
T1  - Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation
DO  - 10.1002/biof.1931
ER  - 

@article{
author = "Zakić, Tamara and Stojanović, Sara and Janković, Aleksandra and Korać, Aleksandra and Peković‐Vaughan, Vanja and Korać, Bato",
year = "2022",
abstract = "Adaptive responses to environmental and physiological challenges, including exposure to low environmental temperature, require extensive structural, redox, and metabolic reprogramming. Detailed molecular mechanisms of such processes in the skin are lacking, especially the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and other closely related redox-sensitive transcription factors Nrf1, Nrf3, and nuclear respiratory factor (NRF1). To investigate the role of Nrf2, we examined redox and metabolic responses in the skin of wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2 KO) at room (RT, 24 ± 1°C) and cold (4 ± 1°C) temperature. Our results demonstrate distinct expression profiles of major enzymes involved in antioxidant defense and key metabolic and mitochondrial pathways in the skin, depending on the functional Nrf2 and/or cold stimulus. Nrf2 KO mice at RT displayed profound alterations in redox, mitochondrial and metabolic responses, generally akin to cold-induced skin responses in WT mice. Immunohistochemical analyses of skin cell compartments (keratinocytes, fibroblasts, hair follicle, and sebaceous gland) and spatial locations (nucleus and cytoplasm) revealed synergistic interactions between members of the Nrf transcription factor family as part of redox-metabolic reprogramming in WT mice upon cold acclimation. In contrast, Nrf2 KO mice at RT showed loss of NRF1 expression and a compensatory activation of Nrf1/Nrf3, which was abolished upon cold, concomitant with blunted redox-metabolic responses. These data show for the first time a novel role for Nrf2 in skin physiology in response to low environmental temperature, with important implications in human connective tissue diseases with altered thermogenic responses.",
journal = "BioFactors",
title = "Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation",
doi = "10.1002/biof.1931"
}

Zakić, T., Stojanović, S., Janković, A., Korać, A., Peković‐Vaughan, V.,& Korać, B.. (2022). Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation. in BioFactors.
https://doi.org/10.1002/biof.1931

Zakić T, Stojanović S, Janković A, Korać A, Peković‐Vaughan V, Korać B. Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation. in BioFactors. 2022;.
doi:10.1002/biof.1931 .

Zakić, Tamara, Stojanović, Sara, Janković, Aleksandra, Korać, Aleksandra, Peković‐Vaughan, Vanja, Korać, Bato, "Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation" in BioFactors (2022),
https://doi.org/10.1002/biof.1931 . .

TY  - CONF
AU  - Zakić, Tamara
AU  - Ninković, Anastasija
AU  - Stojanović, Sara
AU  - Budnar Šoškić, Marta
AU  - Kalezić, Anđelika
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković-Vaughan, Vanja
AU  - Korać, Bato
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5128
AB  - Interscapular brown adipose tissue (IBAT) is a highly metabolically active, thermogenic tissue essential for the maintenance of total energy homeostasis, with a remarkable ability for remodelling in response to exogenous stimuli. Given that nuclear factor erythroid 2-related factor 2 (NRF2) has a pivotal role in redox-metabolic homeostasis, we aimed to investigate its role in IBAT homeostasis under basal conditions or upon cold stimulation. Therefore, we analysed structural and redox-metabolic profiles of IBAT in wild-type (WT) and mice lacking functional Nrf2 (Nrf2KO) maintained at room (RT, 24±1°C) or low temperature (4±1°C). Our results show that both WT and Nrf2KO mice appear to be acclimated to cold, showing characteristics of thermogenically active IBAT, including increased gene and protein expression of uncoupling protein 1 (UCP1). Surprisingly, light and electron microscopy revealed that Nrf2KO mice at RT displayed distinct structural features of activated IBAT, together with the presence of vasodilated blood vessels, while the expression of thermogenic marker UCP1 did not show a corresponding cold-induced change, thus indicating IBAT functional inactivity. This lack of IBAT thermogenic activity in Nrf2KO mice at RT is consistent with its altered redox-metabolic profile, whereby protein expression of the main antioxidant defence and key metabolic enzymes either remained the same or was decreased compared to WT mice at RT. Accordingly, circulatory levels of triglycerides and cholesterol were decreased while glucose, urea and creatinine remained unchanged. Moreover, gene and/or protein expression of important redox-metabolic transcriptional factors – erythroid NRF1, NFkB, PGC-1α and PPARγ, as well as eNOS and AMPKα were increased, suggesting compensatory molecular mechanisms leading to altered IBAT phenotype in Nrf2KO mice at RT. In conclusion, the lack of functional Nrf2 leads to marked structural characteristics of active IBAT in Nrf2KO mice at RT, which are only followed by its functional activation through distinct redox-metabolic reprogramming after cold stimulation.
PB  - Society for Free Radical Research-Europe
C3  - Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
T1  - Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation
DO  - 10.1016/j.freeradbiomed.2022.06.035
SP  - 5
ER  - 

@conference{
author = "Zakić, Tamara and Ninković, Anastasija and Stojanović, Sara and Budnar Šoškić, Marta and Kalezić, Anđelika and Janković, Aleksandra and Korać, Aleksandra and Peković-Vaughan, Vanja and Korać, Bato",
year = "2022",
abstract = "Interscapular brown adipose tissue (IBAT) is a highly metabolically active, thermogenic tissue essential for the maintenance of total energy homeostasis, with a remarkable ability for remodelling in response to exogenous stimuli. Given that nuclear factor erythroid 2-related factor 2 (NRF2) has a pivotal role in redox-metabolic homeostasis, we aimed to investigate its role in IBAT homeostasis under basal conditions or upon cold stimulation. Therefore, we analysed structural and redox-metabolic profiles of IBAT in wild-type (WT) and mice lacking functional Nrf2 (Nrf2KO) maintained at room (RT, 24±1°C) or low temperature (4±1°C). Our results show that both WT and Nrf2KO mice appear to be acclimated to cold, showing characteristics of thermogenically active IBAT, including increased gene and protein expression of uncoupling protein 1 (UCP1). Surprisingly, light and electron microscopy revealed that Nrf2KO mice at RT displayed distinct structural features of activated IBAT, together with the presence of vasodilated blood vessels, while the expression of thermogenic marker UCP1 did not show a corresponding cold-induced change, thus indicating IBAT functional inactivity. This lack of IBAT thermogenic activity in Nrf2KO mice at RT is consistent with its altered redox-metabolic profile, whereby protein expression of the main antioxidant defence and key metabolic enzymes either remained the same or was decreased compared to WT mice at RT. Accordingly, circulatory levels of triglycerides and cholesterol were decreased while glucose, urea and creatinine remained unchanged. Moreover, gene and/or protein expression of important redox-metabolic transcriptional factors – erythroid NRF1, NFkB, PGC-1α and PPARγ, as well as eNOS and AMPKα were increased, suggesting compensatory molecular mechanisms leading to altered IBAT phenotype in Nrf2KO mice at RT. In conclusion, the lack of functional Nrf2 leads to marked structural characteristics of active IBAT in Nrf2KO mice at RT, which are only followed by its functional activation through distinct redox-metabolic reprogramming after cold stimulation.",
publisher = "Society for Free Radical Research-Europe",
journal = "Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium",
title = "Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation",
doi = "10.1016/j.freeradbiomed.2022.06.035",
pages = "5"
}

Zakić, T., Ninković, A., Stojanović, S., Budnar Šoškić, M., Kalezić, A., Janković, A., Korać, A., Peković-Vaughan, V.,& Korać, B.. (2022). Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
Society for Free Radical Research-Europe., 5.
https://doi.org/10.1016/j.freeradbiomed.2022.06.035

Zakić T, Ninković A, Stojanović S, Budnar Šoškić M, Kalezić A, Janković A, Korać A, Peković-Vaughan V, Korać B. Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. 2022;:5.
doi:10.1016/j.freeradbiomed.2022.06.035 .

Zakić, Tamara, Ninković, Anastasija, Stojanović, Sara, Budnar Šoškić, Marta, Kalezić, Anđelika, Janković, Aleksandra, Korać, Aleksandra, Peković-Vaughan, Vanja, Korać, Bato, "Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation" in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium (2022):5,
https://doi.org/10.1016/j.freeradbiomed.2022.06.035 . .

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 . .