TY  - THES
AU  - Kalezić, Anđelika
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4970
AB  - Incidenca premenopauzalnog karcinoma dojke i gojaznosti je u porastu, a veza između ovih oboljenja je izrazito kompleksna. Gojaznost pokazuje negativnu korelaciju sa incidencom premenopauzalnog karcinoma dojke, ali pozitivnu korelaciju sa stopom metastaza, terapijske rezistencije i smrtnosti. Metaboličko reprogramiranje i visoka plastičnost redoks homeostaze su fundamentalne karakteristike malignog fenotipa koje omogućavaju adaptivni odgovor na povišene energetske zahteve i selektivne pritiske poreklom iz tumorske mikrosredine. U karcinomu dojke adipociti su ključni konstituent tumorske mikrosredine, a dvosmerna komunikacija između kancerskih ćelija i adipocita doprinosi proliferativnom i invazivnom potencijalu kancerskih ćelija. Uprkos ovakvim nalazima, in vivo molekulski mehanizmi redoks-senzitivnog metaboličkog reprogramiranja su mahom nepoznati. Cilj ove doktorske disertacije bio je da se okarakteriše redoks i metabolički profil tumorskog i masnog tkiva normalno uhranjenih i gojaznih premenopauzalnih žena sa benignim, odnosno malignim tumorom dojke i identifikuju ključni metabolički putevi i transkripcioni faktori uključeni u redoks-senzitivno metaboličko reprogramiranje. Pokazana povećana ekspresija osnovnih enzima antioksidativne odbrane ukazuje da malignitet indukuje uspostavljanje nove redoks homeostaze, paralelno u tumorskom i masnom tkivu. Diferencijalna ekspresija enzima antioksidativne odbrane i master regulatora redoks homeostaze, nukleusnog faktora-eritroid faktor 2-zavisnog faktora 2 (Nrf2), između normalno uhranjenih i gojaznih žena, ukazuje da gojaznost utiče na uspostavljanje nove redoks homeostaze u tkivima dojke. Simultano sa redoks reprogramiranjem, povećana ekspresija AMP-aktivirane protein kinaze (AMPK), enzima glikolize i pentozofosfatnog puta ukazuje na uspostavljanje AMPK-zavisnog Varburgovog efekta. Posledično, metabolizam glukoze u tumorskom tkivu je usmeren ka glikolizi uz produkciju laktata i pentozofosfatnom putu, dok je u masnom tkivu usmeren prevashodno ka pentozofosfatnom putu, ističući tkivno specifičan karakter Varburgovog efekta. U skladu sa Varburgovim efektom, smanjena ekspresija enzima oksidativne dekarboksilacije piruvata i Krebsovog ciklusa, a povećana ekspresija enzima oksidativne fosforilacije ukazuju da se metabolizam mitohondrija u tumorskom tkivu održava zahvaljujući plastičnosti anaplerotskih puteva. Sa druge strane, povećan broj kopija mitohondrijske DNK, kao i povećana proteinska ekspresija enzima oksidativne dekarboksilacije piruvata, Krebsovog ciklusa i oksidativne fosforilacije ukazuju da je indukcija oksidativnog metabolizma u osnovi metaboličkog reprogramiranja masnog tkiva u malignitetu. Markantne razlike u ekspresiji enzima uključenih u mobilizaciju, β-oksidaciju i de novo sintezu masnih kiselina između normalno uhranjenih i gojaznih premenopauzalnih žena ukazuju da gojaznost utiče na smer metaboličkog reprogramiranja u tumorskom i masnom tkivu dojke. Rezultati ove doktorske disertacije su pokazali da u procesu neoplastične transformacije tumorsko i masno tkivo dojke čine kompleksan pseudo-organ u kome dolazi do uspostavljanja specifičnih redoks i metaboličkih profila u zavisnosti od sistemskih i lokalnih uticaja gojaznosti na tumorsku mikrosredinu u kojoj se razvija karcinom dojke.
AB  - The incidence of premenopausal breast cancer and obesity is rising, while accumulating evidence shows that the relationship between two diseases is highly complex. Obesity shows a negative correlation with the incidence of premenopausal breast cancer but a positive correlation with the rate of metastasis, therapeutic resistance, and mortality. Metabolic reprogramming and high redox homeostasis threshold are fundamental characteristics of the malignant phenotype that enable adaptive responses to increased energy demands and selective pressures imposed by the tumor microenvironment. In breast cancer, adipocytes represent a crucial component of the tumor microenvironment, where two-way communication between cancer cells and adipocytes contributes to cancer cell proliferation and invasion. Despite such findings, in vivo molecular mechanisms of redox-sensitive metabolic reprogramming remain mostly unknown. This doctoral dissertation aimed to characterize the redox and metabolic profile of tumor and adipose tissue of normalweight and obese premenopausal women with benign or malignant breast tumors and identify key metabolic pathways and transcription factors involved in redox-sensitive metabolic reprogramming. Increased expression of main antioxidant defense enzymes was shown, indicating that malignancy contributes to the establishment of new redox homeostasis, both in tumor and adipose tissue. Differential expression of antioxidant defense enzymes and the master regulator of redox hemostasis, the nuclear factor-erythroid factor 2-related factor 2 (Nrf2), between normal-weight and obese women indicates that obesity affects the establishment of new redox homeostasis. Simultaneously with redox reprogramming, increased expression of AMP-activated protein kinase (AMPK), glycolytic, and pentose phosphate pathway enzymes indicates the establishment of an AMPK-dependent Warburg effect. Consequently, glucose metabolism in tumor tissue is directed to glycolysis with lactate production and the pentose phosphate pathway, while in adipose tissue, it is directed primarily to the pentose phosphate pathway, emphasizing the tissue-specific character of the Warburg effect. Consistent with the Warburg effect, decreased expression of pyruvate decarboxylation and Krebs cycle enzymes and increased expression of oxidative phosphorylation enzymes indicate that mitochondrial metabolism in tumor tissue is maintained due to the plasticity of anaplerotic pathways. On the other hand, increased mitochondrial copy number, as well as protein expression of pyruvate decarboxylation, Krebs cycle, and oxidative phosphorylation enzymes indicate that the induction of oxidative metabolism underlies metabolic reprogramming of adipose tissue in malignancy. Striking differences in the expression of enzymes involved in mobilization, β-oxidation, and de novo synthesis of fatty acids between normal-weight and obese premenopausal women indicate that obesity affects the direction of metabolic reprogramming in breast tumor and adipose tissue. This doctoral dissertation showed that in the process of neoplastic transformation, breast tumor and adipose tissue behave as a complex pseudo-organ in which specific redox and metabolic profiles are established, in accordance with the systemic and local influences of obesity on the tumor microenvironment.
PB  - Belgrade: Faculty of Biology, University of Belgrade
T2  - Faculty of Biology, University of Belgrade
T1  - Metabolički i redoks profil ćelija tumora i masnog tkiva dojke premenopauzalnih žena: veza sa gojaznošću
T1  - Metabolic and redox profile of breast tumor and adipose cells in premenopausal women: the relationship with obesity
SP  - 1
EP  - 125
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4970
ER  - 

@phdthesis{
author = "Kalezić, Anđelika",
year = "2022",
abstract = "Incidenca premenopauzalnog karcinoma dojke i gojaznosti je u porastu, a veza između ovih oboljenja je izrazito kompleksna. Gojaznost pokazuje negativnu korelaciju sa incidencom premenopauzalnog karcinoma dojke, ali pozitivnu korelaciju sa stopom metastaza, terapijske rezistencije i smrtnosti. Metaboličko reprogramiranje i visoka plastičnost redoks homeostaze su fundamentalne karakteristike malignog fenotipa koje omogućavaju adaptivni odgovor na povišene energetske zahteve i selektivne pritiske poreklom iz tumorske mikrosredine. U karcinomu dojke adipociti su ključni konstituent tumorske mikrosredine, a dvosmerna komunikacija između kancerskih ćelija i adipocita doprinosi proliferativnom i invazivnom potencijalu kancerskih ćelija. Uprkos ovakvim nalazima, in vivo molekulski mehanizmi redoks-senzitivnog metaboličkog reprogramiranja su mahom nepoznati. Cilj ove doktorske disertacije bio je da se okarakteriše redoks i metabolički profil tumorskog i masnog tkiva normalno uhranjenih i gojaznih premenopauzalnih žena sa benignim, odnosno malignim tumorom dojke i identifikuju ključni metabolički putevi i transkripcioni faktori uključeni u redoks-senzitivno metaboličko reprogramiranje. Pokazana povećana ekspresija osnovnih enzima antioksidativne odbrane ukazuje da malignitet indukuje uspostavljanje nove redoks homeostaze, paralelno u tumorskom i masnom tkivu. Diferencijalna ekspresija enzima antioksidativne odbrane i master regulatora redoks homeostaze, nukleusnog faktora-eritroid faktor 2-zavisnog faktora 2 (Nrf2), između normalno uhranjenih i gojaznih žena, ukazuje da gojaznost utiče na uspostavljanje nove redoks homeostaze u tkivima dojke. Simultano sa redoks reprogramiranjem, povećana ekspresija AMP-aktivirane protein kinaze (AMPK), enzima glikolize i pentozofosfatnog puta ukazuje na uspostavljanje AMPK-zavisnog Varburgovog efekta. Posledično, metabolizam glukoze u tumorskom tkivu je usmeren ka glikolizi uz produkciju laktata i pentozofosfatnom putu, dok je u masnom tkivu usmeren prevashodno ka pentozofosfatnom putu, ističući tkivno specifičan karakter Varburgovog efekta. U skladu sa Varburgovim efektom, smanjena ekspresija enzima oksidativne dekarboksilacije piruvata i Krebsovog ciklusa, a povećana ekspresija enzima oksidativne fosforilacije ukazuju da se metabolizam mitohondrija u tumorskom tkivu održava zahvaljujući plastičnosti anaplerotskih puteva. Sa druge strane, povećan broj kopija mitohondrijske DNK, kao i povećana proteinska ekspresija enzima oksidativne dekarboksilacije piruvata, Krebsovog ciklusa i oksidativne fosforilacije ukazuju da je indukcija oksidativnog metabolizma u osnovi metaboličkog reprogramiranja masnog tkiva u malignitetu. Markantne razlike u ekspresiji enzima uključenih u mobilizaciju, β-oksidaciju i de novo sintezu masnih kiselina između normalno uhranjenih i gojaznih premenopauzalnih žena ukazuju da gojaznost utiče na smer metaboličkog reprogramiranja u tumorskom i masnom tkivu dojke. Rezultati ove doktorske disertacije su pokazali da u procesu neoplastične transformacije tumorsko i masno tkivo dojke čine kompleksan pseudo-organ u kome dolazi do uspostavljanja specifičnih redoks i metaboličkih profila u zavisnosti od sistemskih i lokalnih uticaja gojaznosti na tumorsku mikrosredinu u kojoj se razvija karcinom dojke., The incidence of premenopausal breast cancer and obesity is rising, while accumulating evidence shows that the relationship between two diseases is highly complex. Obesity shows a negative correlation with the incidence of premenopausal breast cancer but a positive correlation with the rate of metastasis, therapeutic resistance, and mortality. Metabolic reprogramming and high redox homeostasis threshold are fundamental characteristics of the malignant phenotype that enable adaptive responses to increased energy demands and selective pressures imposed by the tumor microenvironment. In breast cancer, adipocytes represent a crucial component of the tumor microenvironment, where two-way communication between cancer cells and adipocytes contributes to cancer cell proliferation and invasion. Despite such findings, in vivo molecular mechanisms of redox-sensitive metabolic reprogramming remain mostly unknown. This doctoral dissertation aimed to characterize the redox and metabolic profile of tumor and adipose tissue of normalweight and obese premenopausal women with benign or malignant breast tumors and identify key metabolic pathways and transcription factors involved in redox-sensitive metabolic reprogramming. Increased expression of main antioxidant defense enzymes was shown, indicating that malignancy contributes to the establishment of new redox homeostasis, both in tumor and adipose tissue. Differential expression of antioxidant defense enzymes and the master regulator of redox hemostasis, the nuclear factor-erythroid factor 2-related factor 2 (Nrf2), between normal-weight and obese women indicates that obesity affects the establishment of new redox homeostasis. Simultaneously with redox reprogramming, increased expression of AMP-activated protein kinase (AMPK), glycolytic, and pentose phosphate pathway enzymes indicates the establishment of an AMPK-dependent Warburg effect. Consequently, glucose metabolism in tumor tissue is directed to glycolysis with lactate production and the pentose phosphate pathway, while in adipose tissue, it is directed primarily to the pentose phosphate pathway, emphasizing the tissue-specific character of the Warburg effect. Consistent with the Warburg effect, decreased expression of pyruvate decarboxylation and Krebs cycle enzymes and increased expression of oxidative phosphorylation enzymes indicate that mitochondrial metabolism in tumor tissue is maintained due to the plasticity of anaplerotic pathways. On the other hand, increased mitochondrial copy number, as well as protein expression of pyruvate decarboxylation, Krebs cycle, and oxidative phosphorylation enzymes indicate that the induction of oxidative metabolism underlies metabolic reprogramming of adipose tissue in malignancy. Striking differences in the expression of enzymes involved in mobilization, β-oxidation, and de novo synthesis of fatty acids between normal-weight and obese premenopausal women indicate that obesity affects the direction of metabolic reprogramming in breast tumor and adipose tissue. This doctoral dissertation showed that in the process of neoplastic transformation, breast tumor and adipose tissue behave as a complex pseudo-organ in which specific redox and metabolic profiles are established, in accordance with the systemic and local influences of obesity on the tumor microenvironment.",
publisher = "Belgrade: Faculty of Biology, University of Belgrade",
journal = "Faculty of Biology, University of Belgrade",
title = "Metabolički i redoks profil ćelija tumora i masnog tkiva dojke premenopauzalnih žena: veza sa gojaznošću, Metabolic and redox profile of breast tumor and adipose cells in premenopausal women: the relationship with obesity",
pages = "1-125",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4970"
}

Kalezić, A.. (2022). Metabolički i redoks profil ćelija tumora i masnog tkiva dojke premenopauzalnih žena: veza sa gojaznošću. in Faculty of Biology, University of Belgrade
Belgrade: Faculty of Biology, University of Belgrade., 1-125.
https://hdl.handle.net/21.15107/rcub_ibiss_4970

Kalezić A. Metabolički i redoks profil ćelija tumora i masnog tkiva dojke premenopauzalnih žena: veza sa gojaznošću. in Faculty of Biology, University of Belgrade. 2022;:1-125.
https://hdl.handle.net/21.15107/rcub_ibiss_4970 .

Kalezić, Anđelika, "Metabolički i redoks profil ćelija tumora i masnog tkiva dojke premenopauzalnih žena: veza sa gojaznošću" in Faculty of Biology, University of Belgrade (2022):1-125,
https://hdl.handle.net/21.15107/rcub_ibiss_4970 .

TY  - JOUR
AU  - Korać, Aleksandra
AU  - Srdić-Galić, Biljana
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Korać, Bato
AU  - Janković, Aleksandra
PY  - 2021
UR  - https://doi.org/10.5114/aoms/92118
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4197
AB  - Introduction: Metabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lip-id storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT). Material and methods: Gene and protein expression levels of leptin, adi-ponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and "at risk" groups. Results: Compared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of "at risk" groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of "at risk" obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin. Conclusions: Low adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.
PB  - Termedia Sp. z.o.o.
T2  - Archives of Medical Science
T1  - Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles
IS  - 2
VL  - 17
DO  - 10.5114/aoms/92118
SP  - 323
EP  - 336
ER  - 

@article{
author = "Korać, Aleksandra and Srdić-Galić, Biljana and Stančić, Ana and Otašević, Vesna and Korać, Bato and Janković, Aleksandra",
year = "2021",
abstract = "Introduction: Metabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lip-id storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT). Material and methods: Gene and protein expression levels of leptin, adi-ponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and "at risk" groups. Results: Compared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of "at risk" groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of "at risk" obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin. Conclusions: Low adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.",
publisher = "Termedia Sp. z.o.o.",
journal = "Archives of Medical Science",
title = "Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles",
number = "2",
volume = "17",
doi = "10.5114/aoms/92118",
pages = "323-336"
}

Korać, A., Srdić-Galić, B., Stančić, A., Otašević, V., Korać, B.,& Janković, A.. (2021). Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles. in Archives of Medical Science
Termedia Sp. z.o.o.., 17(2), 323-336.
https://doi.org/10.5114/aoms/92118

Korać A, Srdić-Galić B, Stančić A, Otašević V, Korać B, Janković A. Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles. in Archives of Medical Science. 2021;17(2):323-336.
doi:10.5114/aoms/92118 .

Korać, Aleksandra, Srdić-Galić, Biljana, Stančić, Ana, Otašević, Vesna, Korać, Bato, Janković, Aleksandra, "Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles" in Archives of Medical Science, 17, no. 2 (2021):323-336,
https://doi.org/10.5114/aoms/92118 . .

TY  - JOUR
AU  - Janković, Aleksandra
AU  - Saso, Luciano
AU  - Korać, Aleksandra
AU  - Korać, Bato
PY  - 2019
UR  - https://www.hindawi.com/journals/omcl/2019/2471312/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3285
AB  - Accumulation of oxidative insults on molecular and supramolecular levels could compromise renewal potency and architecture in the aging skin. To examine and compare morphological and ultrastructural changes with redox alterations during chronological skin aging, activities of antioxidant defense (AD) enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), thioredoxin reductase (TR), and methionine sulfoxide reductase A (MsrA), and the markers of oxidative damage of biomolecules—4-hydroxynonenal (HNE) and 8-oxoguanine (8-oxoG)—were examined in the rat skin during life (from 3 days to 21 months). As compared to adult 3-month-old skin, higher activities of CAT, GSH-Px, and GR and a decline in expression of MsrA are found in 21-month-old skin. These changes correspond to degenerative changes at structural and ultrastructural levels in epidermal and dermal compartments, low proliferation capacity, and higher levels of HNE-modified protein aldehydes (particularly in basal lamina) and 8-oxoG positivity in nuclei and mitochondria in the sebaceous glands and root sheath. In 3-day-old skin, higher activities of AD enzymes (SOD, CAT, GR, and TR) and MsrA expression correspond to intensive postnatal development and proliferation. In contrast to 21-month-old skin, a high level of HNE in young skin is not accompanied by 8-oxoG positivity or any morphological disturbances. Observed results indicate that increased activity of AD enzymes in elderly rat skin represents the compensatory response to accumulated oxidative damage of DNA and proteins, accompanied by attenuated repair and proliferative capacity, but in young rats the redox changes are necessary and inherent with processes which occur during postnatal skin development. Мorphological and ultrastructurаl changes are in line with the redox profile in the skin of young and old rats.
T2  - Oxidative Medicine and Cellular Longevity
T1  - Relation of Redox and Structural Alterations of Rat Skin in the Function of Chronological Aging
VL  - 2019
DO  - 10.1155/2019/2471312
SP  - 2471312
ER  - 

@article{
author = "Janković, Aleksandra and Saso, Luciano and Korać, Aleksandra and Korać, Bato",
year = "2019",
abstract = "Accumulation of oxidative insults on molecular and supramolecular levels could compromise renewal potency and architecture in the aging skin. To examine and compare morphological and ultrastructural changes with redox alterations during chronological skin aging, activities of antioxidant defense (AD) enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), thioredoxin reductase (TR), and methionine sulfoxide reductase A (MsrA), and the markers of oxidative damage of biomolecules—4-hydroxynonenal (HNE) and 8-oxoguanine (8-oxoG)—were examined in the rat skin during life (from 3 days to 21 months). As compared to adult 3-month-old skin, higher activities of CAT, GSH-Px, and GR and a decline in expression of MsrA are found in 21-month-old skin. These changes correspond to degenerative changes at structural and ultrastructural levels in epidermal and dermal compartments, low proliferation capacity, and higher levels of HNE-modified protein aldehydes (particularly in basal lamina) and 8-oxoG positivity in nuclei and mitochondria in the sebaceous glands and root sheath. In 3-day-old skin, higher activities of AD enzymes (SOD, CAT, GR, and TR) and MsrA expression correspond to intensive postnatal development and proliferation. In contrast to 21-month-old skin, a high level of HNE in young skin is not accompanied by 8-oxoG positivity or any morphological disturbances. Observed results indicate that increased activity of AD enzymes in elderly rat skin represents the compensatory response to accumulated oxidative damage of DNA and proteins, accompanied by attenuated repair and proliferative capacity, but in young rats the redox changes are necessary and inherent with processes which occur during postnatal skin development. Мorphological and ultrastructurаl changes are in line with the redox profile in the skin of young and old rats.",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Relation of Redox and Structural Alterations of Rat Skin in the Function of Chronological Aging",
volume = "2019",
doi = "10.1155/2019/2471312",
pages = "2471312"
}

Janković, A., Saso, L., Korać, A.,& Korać, B.. (2019). Relation of Redox and Structural Alterations of Rat Skin in the Function of Chronological Aging. in Oxidative Medicine and Cellular Longevity, 2019, 2471312.
https://doi.org/10.1155/2019/2471312

Janković A, Saso L, Korać A, Korać B. Relation of Redox and Structural Alterations of Rat Skin in the Function of Chronological Aging. in Oxidative Medicine and Cellular Longevity. 2019;2019:2471312.
doi:10.1155/2019/2471312 .

Janković, Aleksandra, Saso, Luciano, Korać, Aleksandra, Korać, Bato, "Relation of Redox and Structural Alterations of Rat Skin in the Function of Chronological Aging" in Oxidative Medicine and Cellular Longevity, 2019 (2019):2471312,
https://doi.org/10.1155/2019/2471312 . .

TY  - JOUR
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Buzadžić, Biljana
AU  - Otašević, Vesna
AU  - Korać, Bato
PY  - 2018
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0047637417301252
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2859
AB  - The role of nitric oxide (NO) in cutaneous physiology/pathology became a growing research field since the discovery that almost all types of skin cells can synthetize this redox signaling molecule about 20 years ago. Now, it is evident that NO is an important player in skin physiological processes and in responses of cutaneous cells to external insults, while the impaired NO signaling has an important consequence in skin pathology. Skin disorders are common complications in diabetic conditions. Various metabolic/biochemical and immunological dysregulations in diabetic skin are tightly coupled with the disturbances in the redox state, primarily the ratio between NO and superoxide (O(cyrillic) 2 - ). This review describes possible therapeutic significance of different redox state modulators in the treatment of diabetic skin disorders. The focus is on those modulators that tightly control NO/O(cyrillic) 2 - ratio through the complex mechanisms affecting endogenous NO and O(cyrillic) 2 - producing and removing systems. The fact that classic antioxidants failed to show significant benefits in diabetes, emphasizes the importance of such redox mechanism-based and targeted approaches.
T2  - Mechanisms of Ageing and Development
T1  - The role of nitric oxide in diabetic skin (patho)physiology
VL  - 172
DO  - 10.1016/j.mad.2017.08.018
SP  - 21
EP  - 29
ER  - 

@article{
author = "Stančić, Ana and Janković, Aleksandra and Korać, Aleksandra and Buzadžić, Biljana and Otašević, Vesna and Korać, Bato",
year = "2018",
abstract = "The role of nitric oxide (NO) in cutaneous physiology/pathology became a growing research field since the discovery that almost all types of skin cells can synthetize this redox signaling molecule about 20 years ago. Now, it is evident that NO is an important player in skin physiological processes and in responses of cutaneous cells to external insults, while the impaired NO signaling has an important consequence in skin pathology. Skin disorders are common complications in diabetic conditions. Various metabolic/biochemical and immunological dysregulations in diabetic skin are tightly coupled with the disturbances in the redox state, primarily the ratio between NO and superoxide (O(cyrillic) 2 - ). This review describes possible therapeutic significance of different redox state modulators in the treatment of diabetic skin disorders. The focus is on those modulators that tightly control NO/O(cyrillic) 2 - ratio through the complex mechanisms affecting endogenous NO and O(cyrillic) 2 - producing and removing systems. The fact that classic antioxidants failed to show significant benefits in diabetes, emphasizes the importance of such redox mechanism-based and targeted approaches.",
journal = "Mechanisms of Ageing and Development",
title = "The role of nitric oxide in diabetic skin (patho)physiology",
volume = "172",
doi = "10.1016/j.mad.2017.08.018",
pages = "21-29"
}

Stančić, A., Janković, A., Korać, A., Buzadžić, B., Otašević, V.,& Korać, B.. (2018). The role of nitric oxide in diabetic skin (patho)physiology. in Mechanisms of Ageing and Development, 172, 21-29.
https://doi.org/10.1016/j.mad.2017.08.018

Stančić A, Janković A, Korać A, Buzadžić B, Otašević V, Korać B. The role of nitric oxide in diabetic skin (patho)physiology. in Mechanisms of Ageing and Development. 2018;172:21-29.
doi:10.1016/j.mad.2017.08.018 .

Stančić, Ana, Janković, Aleksandra, Korać, Aleksandra, Buzadžić, Biljana, Otašević, Vesna, Korać, Bato, "The role of nitric oxide in diabetic skin (patho)physiology" in Mechanisms of Ageing and Development, 172 (2018):21-29,
https://doi.org/10.1016/j.mad.2017.08.018 . .

TY  - JOUR
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Ćirović, Duško
AU  - Otašević, Vesna
AU  - Storey, Kenneth B.
AU  - Korać, Bato
PY  - 2018
UR  - http://linkinghub.elsevier.com/retrieve/pii/S1096495918300198
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3011
AB  - In the present study we hypothesized that myocardial adaptive phenotype in mammalian hibernation involves rearrangement of mitochondria bioenergetic pathways providing protective pattern in states of reduced metabolism and low temperature. European ground squirrels (Spermophilus citellus) were exposed to low temperature (4 ± 1 °C) and then divided into two groups: (1) animals that fell into torpor (hibernating group) and (2) animals that stayed active and euthermic for 1, 3, 7, 12, or 21 days (cold-exposed group). Protein levels of selected components of the electron transport chain and ATP synthase in the heart increased after prolonged cold acclimation (mainly from day 7-21 of cold exposure) and during hibernation. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) was also upregulated under both cold exposure and hibernating conditions. The phosphorylation state (Thr172) of 5'-AMP-activated protein kinase α increased early in cold exposure (at day 1 and 3) along with increased protein levels of phosphofructokinase and pyruvate dehydrogenase, whereas hypoxia inducible factor 1α protein levels showed no changes in response to cold exposure or hibernation. Hibernation also resulted in protein upregulation of three antioxidant defense enzymes (manganese and copper/zinc superoxide dismutases and glutathione peroxidase) and thioredoxin in the heart. Cold-exposed and hibernation-related phenotypes of the heart are characterized by improved molecular basis for mitochondrial energy-producing and antioxidant capacities that are achieved in a controlled manner. The recapitulation of such adaptive mechanisms found in hibernators could have broad application for myocardial protection from ishemia/reperfusion to improve hypothermic survival and cold preservation of hearts from non-hibernating species, including humans.
T2  - Comparative Biochemistry and Physiology. B: Biochemistry and Molecular Biology
T1  - A lesson from the oxidative metabolism of hibernator heart: Possible strategy for cardioprotection.
VL  - 219-220
DO  - 10.1016/j.cbpb.2018.02.004
SP  - 1
EP  - 9
ER  - 

@article{
author = "Stančić, Ana and Janković, Aleksandra and Korać, Aleksandra and Ćirović, Duško and Otašević, Vesna and Storey, Kenneth B. and Korać, Bato",
year = "2018",
abstract = "In the present study we hypothesized that myocardial adaptive phenotype in mammalian hibernation involves rearrangement of mitochondria bioenergetic pathways providing protective pattern in states of reduced metabolism and low temperature. European ground squirrels (Spermophilus citellus) were exposed to low temperature (4 ± 1 °C) and then divided into two groups: (1) animals that fell into torpor (hibernating group) and (2) animals that stayed active and euthermic for 1, 3, 7, 12, or 21 days (cold-exposed group). Protein levels of selected components of the electron transport chain and ATP synthase in the heart increased after prolonged cold acclimation (mainly from day 7-21 of cold exposure) and during hibernation. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) was also upregulated under both cold exposure and hibernating conditions. The phosphorylation state (Thr172) of 5'-AMP-activated protein kinase α increased early in cold exposure (at day 1 and 3) along with increased protein levels of phosphofructokinase and pyruvate dehydrogenase, whereas hypoxia inducible factor 1α protein levels showed no changes in response to cold exposure or hibernation. Hibernation also resulted in protein upregulation of three antioxidant defense enzymes (manganese and copper/zinc superoxide dismutases and glutathione peroxidase) and thioredoxin in the heart. Cold-exposed and hibernation-related phenotypes of the heart are characterized by improved molecular basis for mitochondrial energy-producing and antioxidant capacities that are achieved in a controlled manner. The recapitulation of such adaptive mechanisms found in hibernators could have broad application for myocardial protection from ishemia/reperfusion to improve hypothermic survival and cold preservation of hearts from non-hibernating species, including humans.",
journal = "Comparative Biochemistry and Physiology. B: Biochemistry and Molecular Biology",
title = "A lesson from the oxidative metabolism of hibernator heart: Possible strategy for cardioprotection.",
volume = "219-220",
doi = "10.1016/j.cbpb.2018.02.004",
pages = "1-9"
}

Stančić, A., Janković, A., Korać, A., Ćirović, D., Otašević, V., Storey, K. B.,& Korać, B.. (2018). A lesson from the oxidative metabolism of hibernator heart: Possible strategy for cardioprotection.. in Comparative Biochemistry and Physiology. B: Biochemistry and Molecular Biology, 219-220, 1-9.
https://doi.org/10.1016/j.cbpb.2018.02.004

Stančić A, Janković A, Korać A, Ćirović D, Otašević V, Storey KB, Korać B. A lesson from the oxidative metabolism of hibernator heart: Possible strategy for cardioprotection.. in Comparative Biochemistry and Physiology. B: Biochemistry and Molecular Biology. 2018;219-220:1-9.
doi:10.1016/j.cbpb.2018.02.004 .

Stančić, Ana, Janković, Aleksandra, Korać, Aleksandra, Ćirović, Duško, Otašević, Vesna, Storey, Kenneth B., Korać, Bato, "A lesson from the oxidative metabolism of hibernator heart: Possible strategy for cardioprotection." in Comparative Biochemistry and Physiology. B: Biochemistry and Molecular Biology, 219-220 (2018):1-9,
https://doi.org/10.1016/j.cbpb.2018.02.004 . .

TY  - JOUR
AU  - Banjac, Nevena
AU  - Stanišić, Mariana
AU  - Savić, Jelena
AU  - Ćosić, Tatjana
AU  - Stanisavljević, Nemanja
AU  - Miljuš-Đukić, Jovanka
AU  - Marin, Marija
AU  - Radović, Svetlana
AU  - Ninković, Slavica
PY  - 2018
UR  - http://link.springer.com/10.1007/s00709-018-1250-0
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3064
AB  - Chenopodium murale L. is an invasive weed species significantly interfering with wheat crop. However, the complete nature of its allelopathic influence on crops is not yet fully understood. In the present study, the focus is made on establishing the relation between plant morphophysiological changes and oxidative stress, induced by allelopathic extract. Phytotoxic medium of C. murale hairy root clone R5 reduced the germination rate (24% less than control value) of wheat cv. Nataša seeds, as well as seedling growth, diminishing shoot and root length significantly, decreased total chlorophyll content, and induced abnormal root gravitropism. The R5 treatment caused cellular structural abnormalities, reflecting on the root and leaf cell shape and organization. These abnormalities mostly included the increased number of mitochondria and reorganization of the vacuolar compartment, changes in nucleus shape, and chloroplast organization and distribution. The most significant structural changes were observed in cell wall in the form of amoeboid protrusions and folds leading to its irregular shape. These structural alterations were accompanied by an oxidative stress in tissues of treated wheat seedlings, reflected as increased level of H2O2 and other ROS molecules, an increase of radical scavenging capacity and total phenolic content. Accordingly, the retardation of wheat seedling growth by C. murale allelochemicals may represent a consequence of complex activity involving both cell structure alteration and physiological processes.
T2  - Protoplasma
T1  - Physiological and cell ultrastructure disturbances in wheat seedlings generated by Chenopodium murale hairy root exudate.
DO  - 10.1007/s00709-018-1250-0
ER  - 

@article{
author = "Banjac, Nevena and Stanišić, Mariana and Savić, Jelena and Ćosić, Tatjana and Stanisavljević, Nemanja and Miljuš-Đukić, Jovanka and Marin, Marija and Radović, Svetlana and Ninković, Slavica",
year = "2018",
abstract = "Chenopodium murale L. is an invasive weed species significantly interfering with wheat crop. However, the complete nature of its allelopathic influence on crops is not yet fully understood. In the present study, the focus is made on establishing the relation between plant morphophysiological changes and oxidative stress, induced by allelopathic extract. Phytotoxic medium of C. murale hairy root clone R5 reduced the germination rate (24% less than control value) of wheat cv. Nataša seeds, as well as seedling growth, diminishing shoot and root length significantly, decreased total chlorophyll content, and induced abnormal root gravitropism. The R5 treatment caused cellular structural abnormalities, reflecting on the root and leaf cell shape and organization. These abnormalities mostly included the increased number of mitochondria and reorganization of the vacuolar compartment, changes in nucleus shape, and chloroplast organization and distribution. The most significant structural changes were observed in cell wall in the form of amoeboid protrusions and folds leading to its irregular shape. These structural alterations were accompanied by an oxidative stress in tissues of treated wheat seedlings, reflected as increased level of H2O2 and other ROS molecules, an increase of radical scavenging capacity and total phenolic content. Accordingly, the retardation of wheat seedling growth by C. murale allelochemicals may represent a consequence of complex activity involving both cell structure alteration and physiological processes.",
journal = "Protoplasma",
title = "Physiological and cell ultrastructure disturbances in wheat seedlings generated by Chenopodium murale hairy root exudate.",
doi = "10.1007/s00709-018-1250-0"
}

Banjac, N., Stanišić, M., Savić, J., Ćosić, T., Stanisavljević, N., Miljuš-Đukić, J., Marin, M., Radović, S.,& Ninković, S.. (2018). Physiological and cell ultrastructure disturbances in wheat seedlings generated by Chenopodium murale hairy root exudate.. in Protoplasma.
https://doi.org/10.1007/s00709-018-1250-0

Banjac N, Stanišić M, Savić J, Ćosić T, Stanisavljević N, Miljuš-Đukić J, Marin M, Radović S, Ninković S. Physiological and cell ultrastructure disturbances in wheat seedlings generated by Chenopodium murale hairy root exudate.. in Protoplasma. 2018;.
doi:10.1007/s00709-018-1250-0 .

Banjac, Nevena, Stanišić, Mariana, Savić, Jelena, Ćosić, Tatjana, Stanisavljević, Nemanja, Miljuš-Đukić, Jovanka, Marin, Marija, Radović, Svetlana, Ninković, Slavica, "Physiological and cell ultrastructure disturbances in wheat seedlings generated by Chenopodium murale hairy root exudate." in Protoplasma (2018),
https://doi.org/10.1007/s00709-018-1250-0 . .

TY  - JOUR
AU  - Pajević, M.
AU  - Aleksić, M.
AU  - Golić, I.
AU  - Markelić, M.
AU  - Otašević, Vesna
AU  - Janković, Aleksandra
AU  - Stančić, Ana
AU  - Korać, Bato
AU  - Korać, A.
PY  - 2018
UR  - https://journals.viamedica.pl/folia_morphologica/article/view/55303
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3143
AB  - Background: The effect of insulin on the endocrine pancreas has been the subject of extensive study, but quantitative morphometric investigations of the exocrine pancreas are scarce. This study was therefore undertaken to investigate the effect of acute and chronic insulin administration (two doses, 0.4 IU and 4 IU) on the morphology of rat pancreas acini. Materials and methods: Semi-fine sections stained with methylene blue and basic fuchsine or haematoxylin and eosin-stained 5-micrometer thick paraffin sections were used for fractal and stereological analysis of exocrine acini. Acute insulin treatment, independent of applied doses increased fractal dimension in line with decreased lacunarity of pancreas acini. Chronic low dose insulin decreased fractal dimension and increased lacunarity of pancreas acini, but a high dose had the opposite effect. The volume densities (Vv) of cytoplasm, granules and nucleus are affected differently: acute low dose and high chronic dose significantly decreased granules Vv, and in line increased cytoplasmic Vv, whereas other examined structures showed slight changes without statistical significance. Results: The results obtained from this investigation indicate that insulin treatment induced structural remodelling of the exocrine pancreas suggesting a substantial role of insulin in its functioning. Conclusions: Additionally, we showed that fine architectural changes in acini could be detected by fractal analysis, suggesting this method as an alternative or addition to routine stereology.
T2  - Folia Morphologica
T1  - Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling
IS  - 3
VL  - 77
DO  - 10.5603/FM.a2017.0106
SP  - 478
EP  - 484
ER  - 

@article{
author = "Pajević, M. and Aleksić, M. and Golić, I. and Markelić, M. and Otašević, Vesna and Janković, Aleksandra and Stančić, Ana and Korać, Bato and Korać, A.",
year = "2018",
abstract = "Background: The effect of insulin on the endocrine pancreas has been the subject of extensive study, but quantitative morphometric investigations of the exocrine pancreas are scarce. This study was therefore undertaken to investigate the effect of acute and chronic insulin administration (two doses, 0.4 IU and 4 IU) on the morphology of rat pancreas acini. Materials and methods: Semi-fine sections stained with methylene blue and basic fuchsine or haematoxylin and eosin-stained 5-micrometer thick paraffin sections were used for fractal and stereological analysis of exocrine acini. Acute insulin treatment, independent of applied doses increased fractal dimension in line with decreased lacunarity of pancreas acini. Chronic low dose insulin decreased fractal dimension and increased lacunarity of pancreas acini, but a high dose had the opposite effect. The volume densities (Vv) of cytoplasm, granules and nucleus are affected differently: acute low dose and high chronic dose significantly decreased granules Vv, and in line increased cytoplasmic Vv, whereas other examined structures showed slight changes without statistical significance. Results: The results obtained from this investigation indicate that insulin treatment induced structural remodelling of the exocrine pancreas suggesting a substantial role of insulin in its functioning. Conclusions: Additionally, we showed that fine architectural changes in acini could be detected by fractal analysis, suggesting this method as an alternative or addition to routine stereology.",
journal = "Folia Morphologica",
title = "Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling",
number = "3",
volume = "77",
doi = "10.5603/FM.a2017.0106",
pages = "478-484"
}

Pajević, M., Aleksić, M., Golić, I., Markelić, M., Otašević, V., Janković, A., Stančić, A., Korać, B.,& Korać, A.. (2018). Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling. in Folia Morphologica, 77(3), 478-484.
https://doi.org/10.5603/FM.a2017.0106

Pajević M, Aleksić M, Golić I, Markelić M, Otašević V, Janković A, Stančić A, Korać B, Korać A. Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling. in Folia Morphologica. 2018;77(3):478-484.
doi:10.5603/FM.a2017.0106 .

Pajević, M., Aleksić, M., Golić, I., Markelić, M., Otašević, Vesna, Janković, Aleksandra, Stančić, Ana, Korać, Bato, Korać, A., "Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling" in Folia Morphologica, 77, no. 3 (2018):478-484,
https://doi.org/10.5603/FM.a2017.0106 . .

TY  - JOUR
AU  - Stančić, Ana
AU  - Korać, Aleksandra
AU  - Otašević, Vesna
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2018
UR  - http://hrana-ishrana.org/wp-content/uploads/2019/01/Hrana-i-ishrana-59-br-1.pdf
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3318
AB  - Growing evidences suggest that statins exert several cholesterol-independent pleiotropic effects in diabetes, but there is no consensus whether they are positive or negative. To shed more light on this issue, we examined the effect of simvastatin on β-cell regeneration in a diabetic state. Diabetes was induced in male Mill Hill rats with a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were additionally separated into two subgroups: treated with simvastatin (5 mg/kg/day, i.g., 12 days) and control. Treatment of diabetic animals started after diabetes induction (glucose level ≥ 12 mmol/L). Our findings revealed that there is no increase in the area of insulin-immunopositive cells neither normalization of serum insulin level after simvastatin treatment of diabetic animals, although simvastatin increased nuclear immunopositivity for pancreas duodenum homeobox-1 (PDX-1) and proliferating cell nuclear antigen (PCNA). The data from this study suggest that 12-day treatment with simvastatin did not improve diabetes- induced disturbances in β-cell mass/function.
T2  - Hrana i Ishrana
T1  - The effect of simvastatin in pancreas of diabetic rats
IS  - 1
VL  - 59
SP  - 19
EP  - 25
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3318
ER  - 

@article{
author = "Stančić, Ana and Korać, Aleksandra and Otašević, Vesna and Janković, Aleksandra and Korać, Bato",
year = "2018",
abstract = "Growing evidences suggest that statins exert several cholesterol-independent pleiotropic effects in diabetes, but there is no consensus whether they are positive or negative. To shed more light on this issue, we examined the effect of simvastatin on β-cell regeneration in a diabetic state. Diabetes was induced in male Mill Hill rats with a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were additionally separated into two subgroups: treated with simvastatin (5 mg/kg/day, i.g., 12 days) and control. Treatment of diabetic animals started after diabetes induction (glucose level ≥ 12 mmol/L). Our findings revealed that there is no increase in the area of insulin-immunopositive cells neither normalization of serum insulin level after simvastatin treatment of diabetic animals, although simvastatin increased nuclear immunopositivity for pancreas duodenum homeobox-1 (PDX-1) and proliferating cell nuclear antigen (PCNA). The data from this study suggest that 12-day treatment with simvastatin did not improve diabetes- induced disturbances in β-cell mass/function.",
journal = "Hrana i Ishrana",
title = "The effect of simvastatin in pancreas of diabetic rats",
number = "1",
volume = "59",
pages = "19-25",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3318"
}

Stančić, A., Korać, A., Otašević, V., Janković, A.,& Korać, B.. (2018). The effect of simvastatin in pancreas of diabetic rats. in Hrana i Ishrana, 59(1), 19-25.
https://hdl.handle.net/21.15107/rcub_ibiss_3318

Stančić A, Korać A, Otašević V, Janković A, Korać B. The effect of simvastatin in pancreas of diabetic rats. in Hrana i Ishrana. 2018;59(1):19-25.
https://hdl.handle.net/21.15107/rcub_ibiss_3318 .

Stančić, Ana, Korać, Aleksandra, Otašević, Vesna, Janković, Aleksandra, Korać, Bato, "The effect of simvastatin in pancreas of diabetic rats" in Hrana i Ishrana, 59, no. 1 (2018):19-25,
https://hdl.handle.net/21.15107/rcub_ibiss_3318 .

TY  - JOUR
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Buzadžić, Biljana
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Ferdinandy, Peter
AU  - Daiber, Andreas
AU  - Korać, Bato
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6734
AB  - Insulin sensitivity and metabolic homeostasis depend on the capacity of adipose tissue to take up and utilize excess glucose and fatty acids. The key aspects that determine the fuel‐buffering capacity of adipose tissue depend on the physiological levels of the small redox molecule, nitric oxide (NO). In addition to impairment of NO synthesis, excessive formation of the superoxide anion (О2 •–) in adipose tissue may be an important interfering factor diverting the signalling of NO and other reactive oxygen and nitrogen species in obesity, resulting in metabolic dysfunction of adipose tissue over time. Besides its role in relief from superoxide burst, enhanced NO signalling may be responsible for the therapeutic benefits of different superoxide dismutase mimetics, in obesity and experimental diabetes models. This review summarizes the role of NO in adipose tissue and highlights the effects of NO/О2 •– ratio ‘teetering’ as a promising pharmacological target in the metabolic syndrome.
PB  - John Wiley & Sons, Inc
T2  - British Journal of Pharmacology
T1  - Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management
IS  - 12
VL  - 174
DO  - 10.1111/bph.13498
SP  - 1570
EP  - 1590
ER  - 

@article{
author = "Janković, Aleksandra and Korać, Aleksandra and Buzadžić, Biljana and Stančić, Ana and Otašević, Vesna and Ferdinandy, Peter and Daiber, Andreas and Korać, Bato",
year = "2017",
abstract = "Insulin sensitivity and metabolic homeostasis depend on the capacity of adipose tissue to take up and utilize excess glucose and fatty acids. The key aspects that determine the fuel‐buffering capacity of adipose tissue depend on the physiological levels of the small redox molecule, nitric oxide (NO). In addition to impairment of NO synthesis, excessive formation of the superoxide anion (О2 •–) in adipose tissue may be an important interfering factor diverting the signalling of NO and other reactive oxygen and nitrogen species in obesity, resulting in metabolic dysfunction of adipose tissue over time. Besides its role in relief from superoxide burst, enhanced NO signalling may be responsible for the therapeutic benefits of different superoxide dismutase mimetics, in obesity and experimental diabetes models. This review summarizes the role of NO in adipose tissue and highlights the effects of NO/О2 •– ratio ‘teetering’ as a promising pharmacological target in the metabolic syndrome.",
publisher = "John Wiley & Sons, Inc",
journal = "British Journal of Pharmacology",
title = "Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management",
number = "12",
volume = "174",
doi = "10.1111/bph.13498",
pages = "1570-1590"
}

Janković, A., Korać, A., Buzadžić, B., Stančić, A., Otašević, V., Ferdinandy, P., Daiber, A.,& Korać, B.. (2017). Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management. in British Journal of Pharmacology
John Wiley & Sons, Inc., 174(12), 1570-1590.
https://doi.org/10.1111/bph.13498

Janković A, Korać A, Buzadžić B, Stančić A, Otašević V, Ferdinandy P, Daiber A, Korać B. Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management. in British Journal of Pharmacology. 2017;174(12):1570-1590.
doi:10.1111/bph.13498 .

Janković, Aleksandra, Korać, Aleksandra, Buzadžić, Biljana, Stančić, Ana, Otašević, Vesna, Ferdinandy, Peter, Daiber, Andreas, Korać, Bato, "Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management" in British Journal of Pharmacology, 174, no. 12 (2017):1570-1590,
https://doi.org/10.1111/bph.13498 . .

TY  - JOUR
AU  - Stančić, Ana
AU  - Filipović, Miloš
AU  - Ivanović-Burmazović, Ivana
AU  - Mašović, Sava
AU  - Janković, Aleksandra
AU  - Otašević, Vesna
AU  - Korać, Aleksandra
AU  - Buzadžić, Biljana
AU  - Korać, Bato
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0009279717300030
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2766
AB  - Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, L-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with L-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that L-arginine and M40403 restored diabetes-induced impairment of phospho-5′-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, L-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of L-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that L-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease.
T2  - Chemico-Biological Interactions
T1  - Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l -arginine and SOD mimic
VL  - 272
DO  - 10.1016/j.cbi.2017.05.003
SP  - 188
EP  - 196
ER  - 

@article{
author = "Stančić, Ana and Filipović, Miloš and Ivanović-Burmazović, Ivana and Mašović, Sava and Janković, Aleksandra and Otašević, Vesna and Korać, Aleksandra and Buzadžić, Biljana and Korać, Bato",
year = "2017",
abstract = "Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, L-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with L-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that L-arginine and M40403 restored diabetes-induced impairment of phospho-5′-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, L-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of L-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that L-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease.",
journal = "Chemico-Biological Interactions",
title = "Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l -arginine and SOD mimic",
volume = "272",
doi = "10.1016/j.cbi.2017.05.003",
pages = "188-196"
}

Stančić, A., Filipović, M., Ivanović-Burmazović, I., Mašović, S., Janković, A., Otašević, V., Korać, A., Buzadžić, B.,& Korać, B.. (2017). Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l -arginine and SOD mimic. in Chemico-Biological Interactions, 272, 188-196.
https://doi.org/10.1016/j.cbi.2017.05.003

Stančić A, Filipović M, Ivanović-Burmazović I, Mašović S, Janković A, Otašević V, Korać A, Buzadžić B, Korać B. Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l -arginine and SOD mimic. in Chemico-Biological Interactions. 2017;272:188-196.
doi:10.1016/j.cbi.2017.05.003 .

Stančić, Ana, Filipović, Miloš, Ivanović-Burmazović, Ivana, Mašović, Sava, Janković, Aleksandra, Otašević, Vesna, Korać, Aleksandra, Buzadžić, Biljana, Korać, Bato, "Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l -arginine and SOD mimic" in Chemico-Biological Interactions, 272 (2017):188-196,
https://doi.org/10.1016/j.cbi.2017.05.003 . .

TY  - JOUR
AU  - Janković, Aleksandra
AU  - Ferreri, Carla
AU  - Filipović, Miloš
AU  - Ivanović-Burmazović, Ivana
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Korać, Aleksandra
AU  - Buzadžić, Biljana
AU  - Korać, Bato
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6211
AB  - Setting the correct ratio of superoxide anion (O2•-) and nitric oxide (•NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of •NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l -1) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.
PB  - Taylor & Francis
T2  - Free Radical Research
T1  - Targeting the superoxide/nitric oxide ratio by L arginine and SOD mimic in rat diabetic skin
IS  - Sup1
VL  - 50
DO  - 10.1080/10715762.2016.1232483
SP  - S51
EP  - S63
ER  - 

@article{
author = "Janković, Aleksandra and Ferreri, Carla and Filipović, Miloš and Ivanović-Burmazović, Ivana and Stančić, Ana and Otašević, Vesna and Korać, Aleksandra and Buzadžić, Biljana and Korać, Bato",
year = "2016",
abstract = "Setting the correct ratio of superoxide anion (O2•-) and nitric oxide (•NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of •NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l -1) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.",
publisher = "Taylor & Francis",
journal = "Free Radical Research",
title = "Targeting the superoxide/nitric oxide ratio by L arginine and SOD mimic in rat diabetic skin",
number = "Sup1",
volume = "50",
doi = "10.1080/10715762.2016.1232483",
pages = "S51-S63"
}

Janković, A., Ferreri, C., Filipović, M., Ivanović-Burmazović, I., Stančić, A., Otašević, V., Korać, A., Buzadžić, B.,& Korać, B.. (2016). Targeting the superoxide/nitric oxide ratio by L arginine and SOD mimic in rat diabetic skin. in Free Radical Research
Taylor & Francis., 50(Sup1), S51-S63.
https://doi.org/10.1080/10715762.2016.1232483

Janković A, Ferreri C, Filipović M, Ivanović-Burmazović I, Stančić A, Otašević V, Korać A, Buzadžić B, Korać B. Targeting the superoxide/nitric oxide ratio by L arginine and SOD mimic in rat diabetic skin. in Free Radical Research. 2016;50(Sup1):S51-S63.
doi:10.1080/10715762.2016.1232483 .

Janković, Aleksandra, Ferreri, Carla, Filipović, Miloš, Ivanović-Burmazović, Ivana, Stančić, Ana, Otašević, Vesna, Korać, Aleksandra, Buzadžić, Biljana, Korać, Bato, "Targeting the superoxide/nitric oxide ratio by L arginine and SOD mimic in rat diabetic skin" in Free Radical Research, 50, no. Sup1 (2016):S51-S63,
https://doi.org/10.1080/10715762.2016.1232483 . .

TY  - JOUR
AU  - Hmaid, Amal AAA
AU  - Markelić, Milica
AU  - Otašević, Vesna
AU  - Mašović, Sava
AU  - Janković, Aleksandra
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6212
AB  - Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (Nω-nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.
PB  - Elsevier
T2  - Saudi Journal of Biological Sciences
T1  - Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation
IS  - 3
VL  - 25
DO  - 10.1016/j.sjbs.2016.01.022
SP  - 537
EP  - 544
ER  - 

@article{
author = "Hmaid, Amal AAA and Markelić, Milica and Otašević, Vesna and Mašović, Sava and Janković, Aleksandra and Korać, Bato and Korać, Aleksandra",
year = "2016",
abstract = "Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (Nω-nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.",
publisher = "Elsevier",
journal = "Saudi Journal of Biological Sciences",
title = "Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation",
number = "3",
volume = "25",
doi = "10.1016/j.sjbs.2016.01.022",
pages = "537-544"
}

Hmaid, A. A., Markelić, M., Otašević, V., Mašović, S., Janković, A., Korać, B.,& Korać, A.. (2016). Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation. in Saudi Journal of Biological Sciences
Elsevier., 25(3), 537-544.
https://doi.org/10.1016/j.sjbs.2016.01.022

Hmaid AA, Markelić M, Otašević V, Mašović S, Janković A, Korać B, Korać A. Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation. in Saudi Journal of Biological Sciences. 2016;25(3):537-544.
doi:10.1016/j.sjbs.2016.01.022 .

Hmaid, Amal AAA, Markelić, Milica, Otašević, Vesna, Mašović, Sava, Janković, Aleksandra, Korać, Bato, Korać, Aleksandra, "Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation" in Saudi Journal of Biological Sciences, 25, no. 3 (2016):537-544,
https://doi.org/10.1016/j.sjbs.2016.01.022 . .

TY  - JOUR
AU  - Janković, Aleksandra
AU  - Korac, Aleksandra
AU  - Buzadžić, Biljana J.
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Daiber, Andreas
AU  - Korać, Bato
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2326
AB  - Obesity is an energy balance disorder associated with dyslipidemia,
   insulin resistance and diabetes type 2, also summarized with the term
   metabolic syndrome or syndrome X. Increasing evidence points to
   ``adipocyte dysfunction{''}, rather than fat mass accretion per se, as
   the key pathophysiological factor for metabolic complications in
   obesity. The dysfunctional fat tissue in obesity characterizes a failure
   to safely store metabolic substrates into existing hypertrophied
   adipocytes and/or into new preadipocytes recruited for differentiation.
   In this review we briefly summarize the potential of redox imbalance in
   fat tissue as an instigator of adipocyte dysfunction in obesity. We
   reveal the challenge of the adipose redox changes, insights in the
   regulation of healthy expansion of adipose tissue and its reduction,
   leading to glucose and lipids overflow. (C) 2015 Published by Elsevier
   B.V.
T2  - Redox Biology
T1  - Redox implications in adipose tissue (dys)function-A new look at old
 acquaintances
VL  - 6
DO  - 10.1016/j.redox.2015.06.018
SP  - 19
EP  - 32
ER  - 

@article{
author = "Janković, Aleksandra and Korac, Aleksandra and Buzadžić, Biljana J. and Otašević, Vesna and Stančić, Ana and Daiber, Andreas and Korać, Bato",
year = "2015",
abstract = "Obesity is an energy balance disorder associated with dyslipidemia,
   insulin resistance and diabetes type 2, also summarized with the term
   metabolic syndrome or syndrome X. Increasing evidence points to
   ``adipocyte dysfunction{''}, rather than fat mass accretion per se, as
   the key pathophysiological factor for metabolic complications in
   obesity. The dysfunctional fat tissue in obesity characterizes a failure
   to safely store metabolic substrates into existing hypertrophied
   adipocytes and/or into new preadipocytes recruited for differentiation.
   In this review we briefly summarize the potential of redox imbalance in
   fat tissue as an instigator of adipocyte dysfunction in obesity. We
   reveal the challenge of the adipose redox changes, insights in the
   regulation of healthy expansion of adipose tissue and its reduction,
   leading to glucose and lipids overflow. (C) 2015 Published by Elsevier
   B.V.",
journal = "Redox Biology",
title = "Redox implications in adipose tissue (dys)function-A new look at old
 acquaintances",
volume = "6",
doi = "10.1016/j.redox.2015.06.018",
pages = "19-32"
}

Janković, A., Korac, A., Buzadžić, B. J., Otašević, V., Stančić, A., Daiber, A.,& Korać, B.. (2015). Redox implications in adipose tissue (dys)function-A new look at old
 acquaintances. in Redox Biology, 6, 19-32.
https://doi.org/10.1016/j.redox.2015.06.018

Janković A, Korac A, Buzadžić BJ, Otašević V, Stančić A, Daiber A, Korać B. Redox implications in adipose tissue (dys)function-A new look at old
 acquaintances. in Redox Biology. 2015;6:19-32.
doi:10.1016/j.redox.2015.06.018 .

Janković, Aleksandra, Korac, Aleksandra, Buzadžić, Biljana J., Otašević, Vesna, Stančić, Ana, Daiber, Andreas, Korać, Bato, "Redox implications in adipose tissue (dys)function-A new look at old
 acquaintances" in Redox Biology, 6 (2015):19-32,
https://doi.org/10.1016/j.redox.2015.06.018 . .

TY  - JOUR
AU  - Veličković, Ksenija
AU  - Čvoro, Aleksandra
AU  - Srdić, Biljana
AU  - Stokić, Edita
AU  - Markelić, Milica
AU  - Golić, Igor
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Buzadžić, Biljana J.
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2294
AB  - Context: Brown adipose tissue (BAT) has the unique ability of generating
   heat due to the expression of mitochondrial uncoupling protein 1 (UCP1).
   A recent discovery regarding functional BAT in adult humans has
   increased interest in the molecular pathways of BAT development and
   functionality. An important role for estrogen in white adipose tissue
   was shown, but the possible role of estrogen in human fetal BAT (fBAT)
   is unclear.
   Objective: The objective of this study was to determine whether human
   fBAT expresses estrogen receptor alpha (ER alpha) and ER beta. In
   addition, we examined their localization as well as their correlation
   with crucial proteins involved in BAT differentiation, proliferation,
   mitochondriogenesis and thermogenesis including peroxisome
   proliferator-activated receptor gamma (PPAR gamma), proliferating cell
   nuclear antigen (PCNA), PPAR gamma-coactivator-1 alpha (PGC-1 alpha),
   and UCP1.
   Design: The fBAT was obtained from 4 human male fetuses aged 15, 17, 20,
   and 23 weeks gestation. ER alpha and ER beta expression was assessed
   using Western blotting, immunohistochemistry, and immunocytochemistry.
   Possible correlations with PPAR gamma, PCNA, PGC-1 alpha, and UCP1 were
   examined by double immunofluorescence.
   Results: Both ER alpha and ER beta were expressed in human fBAT, with ER
   alpha being dominant. Unlike ER beta, which was present only in mature
   brown adipocytes, we detected ER alpha in mature adipocytes,
   preadipocytes, mesenchymal and endothelial cells. In addition, double
   immunofluorescence supported the notion that differentiation in fBAT
   probably involves ER alpha. Immunocytochemical analysis revealed
   mitochondrial localization of both receptors.
   Conclusion: The expression of both ER alpha and ER beta in human fBAT
   suggests a role for estrogen in its development, primarily via ER alpha.
   In addition, our results indicate that fBAT mitochondria could be
   targeted by estrogens and pointed out the possible role of both ERs in
   mitochondriogenesis.
T2  - Journal of Clinical Endocrinology & Metabolism
T1  - Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue
IS  - 1
VL  - 99
DO  - 10.1210/jc.2013-2017
SP  - 151
EP  - 159
ER  - 

@article{
author = "Veličković, Ksenija and Čvoro, Aleksandra and Srdić, Biljana and Stokić, Edita and Markelić, Milica and Golić, Igor and Otašević, Vesna and Stančić, Ana and Janković, Aleksandra and Vučetić, Milica and Buzadžić, Biljana J. and Korać, Bato and Korać, Aleksandra",
year = "2014",
abstract = "Context: Brown adipose tissue (BAT) has the unique ability of generating
   heat due to the expression of mitochondrial uncoupling protein 1 (UCP1).
   A recent discovery regarding functional BAT in adult humans has
   increased interest in the molecular pathways of BAT development and
   functionality. An important role for estrogen in white adipose tissue
   was shown, but the possible role of estrogen in human fetal BAT (fBAT)
   is unclear.
   Objective: The objective of this study was to determine whether human
   fBAT expresses estrogen receptor alpha (ER alpha) and ER beta. In
   addition, we examined their localization as well as their correlation
   with crucial proteins involved in BAT differentiation, proliferation,
   mitochondriogenesis and thermogenesis including peroxisome
   proliferator-activated receptor gamma (PPAR gamma), proliferating cell
   nuclear antigen (PCNA), PPAR gamma-coactivator-1 alpha (PGC-1 alpha),
   and UCP1.
   Design: The fBAT was obtained from 4 human male fetuses aged 15, 17, 20,
   and 23 weeks gestation. ER alpha and ER beta expression was assessed
   using Western blotting, immunohistochemistry, and immunocytochemistry.
   Possible correlations with PPAR gamma, PCNA, PGC-1 alpha, and UCP1 were
   examined by double immunofluorescence.
   Results: Both ER alpha and ER beta were expressed in human fBAT, with ER
   alpha being dominant. Unlike ER beta, which was present only in mature
   brown adipocytes, we detected ER alpha in mature adipocytes,
   preadipocytes, mesenchymal and endothelial cells. In addition, double
   immunofluorescence supported the notion that differentiation in fBAT
   probably involves ER alpha. Immunocytochemical analysis revealed
   mitochondrial localization of both receptors.
   Conclusion: The expression of both ER alpha and ER beta in human fBAT
   suggests a role for estrogen in its development, primarily via ER alpha.
   In addition, our results indicate that fBAT mitochondria could be
   targeted by estrogens and pointed out the possible role of both ERs in
   mitochondriogenesis.",
journal = "Journal of Clinical Endocrinology & Metabolism",
title = "Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue",
number = "1",
volume = "99",
doi = "10.1210/jc.2013-2017",
pages = "151-159"
}

Veličković, K., Čvoro, A., Srdić, B., Stokić, E., Markelić, M., Golić, I., Otašević, V., Stančić, A., Janković, A., Vučetić, M., Buzadžić, B. J., Korać, B.,& Korać, A.. (2014). Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue. in Journal of Clinical Endocrinology & Metabolism, 99(1), 151-159.
https://doi.org/10.1210/jc.2013-2017

Veličković K, Čvoro A, Srdić B, Stokić E, Markelić M, Golić I, Otašević V, Stančić A, Janković A, Vučetić M, Buzadžić BJ, Korać B, Korać A. Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue. in Journal of Clinical Endocrinology & Metabolism. 2014;99(1):151-159.
doi:10.1210/jc.2013-2017 .

Veličković, Ksenija, Čvoro, Aleksandra, Srdić, Biljana, Stokić, Edita, Markelić, Milica, Golić, Igor, Otašević, Vesna, Stančić, Ana, Janković, Aleksandra, Vučetić, Milica, Buzadžić, Biljana J., Korać, Bato, Korać, Aleksandra, "Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue" in Journal of Clinical Endocrinology & Metabolism, 99, no. 1 (2014):151-159,
https://doi.org/10.1210/jc.2013-2017 . .

TY  - THES
AU  - Vučetić, Milica M.
PY  - 2014
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=1104
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:7844/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024705714
UR  - http://nardus.mpn.gov.rs/123456789/2163
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2430
AB  - Fenomen hibernacije predstavlja fascinantan primer plastičnosti kod sisara. Hibernirajući sisari podliježu složenom nizu biohemijskih, fizioloških i bihevioralnih promjena u odgovoru na senzonske energetski-zahtijevne periode kuplovane sa redukovanom dopstupnošću hrane. Cilj disertacije je da se ispitaju promjene ćelijskog metabolizma u tkivima i organima tekunica, ključnim za održanje ukupne energetske homeostaze - mrko i bijelo masno tkivo (engl. brown adipose tissue, BAT i white adipose tissue, WAT), mišići i jetra, tokom perioda aklimacije na nisku temperaturu, kao i u fazi hibernacije.
Efekat aklimacije/hibernacije na metaboličko remodeliranje u tkivima i organima tekunica praćen je određivanjem: mitohondrijalnog kapaciteta (genska i/ili proteinska ekspresije komponenti respiratornog lanca i ATP sintaze); termogenog kapaciteta (ekspresija dekuplujućeg proteina 1); ekspresionih profila enzima ključnih metaboličkih puteva: glikolize, β-oksidacije, Krebsovog ciklusa, metabolizama triacilglicerola i glikogena. Ispitivani su i transkripcioni faktori uključeni u metaboličku regulaciju, kao i enzimi antioksidativne odbrane. Takođe, ispitivane su promjene u BAT i depoima WAT na strukturnom i ultrastrukturnom nivou.
Mužjaci evropske tekunice Spermophilus citellus su početkom septembra podijeljeni u dvije grupe: kontrolnu, koja je boravila na sobnoj temeraturi (22 ± 1 ºC) i grupu aklimiranu na nisku temperaturu (4 ± 1 ºC). Aktivne, eutermične tekunice, koje nisu ušle u duboku hibernaciju tokom aklimacije, žrtvovane su nakon 1, 3, 7, 12, odnosno 21 dan. Tekunice koje su ušle u hibernaciju žrtvovane su nakon 2-5 dana trajanja hibernacije (kontinuirana rektalna temperatura 4 ºC). BAT, subkutano, retroperitonealno i epididimalno WAT (sWAT, rWAT i eWAT), skeletni mišić (musculus quadriceps) i jetra su uzorkovani odmah po žrtvovanju. Kako bi se ispitali mehanizmi metaboličke regulacije u BAT, specifični za hibernatore, paralelno je rađena komparativna studija aklimacije pacova na nisku temperaturu.
Rezultati pokazuju da je, prilikom izlaganja hibernirajućih životinja niskoj temperaturi, ćelijski metabolizam u svim ispitivanim tkivima/organima inicijalno podređen održanju eutermije, tj. termogenom procesu koji se odvija u skeletnim mišićima i BAT. U ranom periodu izlaganja hladnoći, u skeletnim mišićima i BAT, dolazi do indukcije termogeneze (drhteće i nedrhteće), koja je metabolički podržana razlaganjem šećera. Međutim, produkcija toplote u oba termogena organa asocirana je sa energetskim disbalansom, koji je tokom produžene aklimacije najvjerovatnije odgovoran za supresiju puteva potrošnje energije (primarno termogeneze) i pripremu tekunica za ulazak u stanje hipotermije/hipometabolizma. Najveći dio goriva za termogenezu, u ranoj fazi aklimacije, obezbijeđuje se iz visceralnih depoa WAT (posebno eWAT), u kojima je detektovano smanjenje površine adipocitnog profila, usled intenzivne lipolize. Kasnije tokom izlaganja hladnoći, kada se termogeni kapacitet BAT suprimira, u sva tri ispitivana depoa WAT indukovana je aktivnost AMP-aktivirane protein kinase (AMPK), „blokirana” lipoliza i putevi potrošnje energije, a stimulisan oksidativni metabolizam. Jetra tokom aklimacije ima centralno mjesto koordinacije lipidnog i ugljenohidratnog metabolizma.
Rezultati disertacije pokazuju da je u fazi duboke hibernacije termogeni kapacitet BAT i skeletnih mišića značajno suprimiran. Takođe, hipoksija-inducibilni factor-1 (HIF-1) ima centralnu ulogu u metaboličkom remodeliranju termogenih organa u fazi hibernacije. Osim suprimiranja energetski-zahtijevnih termogenih procesa, HIF-1 u uslovima hipometabolizma ima ulogu i u regulaciji, tj. indukciji glikolitičkog puta, važne komponente energetske homeostaze tokom hibernacije. Slično reprogramiranje metabolizma dešava se i u visceralnim depoima WAT. Jetra u hibernaciji ostvaruje veoma sličnu metaboličku strategiju kao pri uslovima gladovanja: indukcija katabolizma lipida i supresija razlaganja glukoze, uz istovremenu indukciju glukoneogeneze.
Rezultati disertacije ukazuju da je u hibernaciji kapacitet za oksidaciju lipida povećan u svim ispitivanim tkivima/organima, osim u visceralnim depoima WAT. U BAT, intenziviranje puteva oksidacije masnih kiselina primarno služi održanju neophodnog nivoa termogeneze, dok je u skeletnim mišićima i jetri povezano sa adaptacijom na hipotermične/hipometaboličke uslove hibernacije. Uočljuv manji stepen interorganske komunikacije kada je lipidni metabolizam u pitanju, sugeriše da se tokom hibernacije uspostavlja određeni stepen tkivne autonomnosti.
Generalno se može zaključiti da karakteristično tkivno-zavisno remodelovanje energetskog metabolizma predstavlja centralnu osovinu i uslov fiziološke plastičnosti
hibernatora koja im omogućava brojne prednosti u odnosu na nehibernirajuće srodnike i preživljavanje u nepovoljnim uslovima sredine, bilo da su aktivni i eutermični ili letargični i hipotemični.
AB  - The phenomenon of hibernation is a fascinating example of plasticity in mammals. Hibernating mammals are subjected to a complex series of biochemical, physiological and behavioral changes in response to seasonal energy-demanding periods coupled with reduced food availability. The aim of the thesis was to investigate metabolic changes in the key tissues and organs of the ground squirrel, responsible for maintaining overall energy homeostasis - brown and white adipose tissue (BAT and WAT), skeletal muscle and liver, during the acclimation to low temperature, as well as in the hibernation.
Effects of acclimation/hibernation on metabolic remodeling in the tissues and organs of the ground squirrel were determined by: mitochondrial capacity (gene and/or protein expression of the components of the respiratory chain and ATP synthase); thermogenic capacity (uncoupling protein 1 content), the expression profile of the key metabolic enzymes involved in: glycolysis, β-oxidation, Krebs cycle, glycogen and triglycerides metabolism. Furthermore, transcription factors involved in the metabolic regulation, as well as antioxidant enzymes, were examined. In parallel, we examined the changes in BAT and WAT depots on the structural and ultrastructural level.
Males of the European ground squirrel Spermophilus citellus were divided into two groups in early September: the control group, kept at room temperature (22 ± 1 º C) and a group acclimated to low temperature (4 ± 1 ºC). Active, euthermic ground squirrels, which did not enter into deep hibernation during acclimation, were sacrificed after 1, 3, 7, 12, or 21 days. Ground squirrels that entered hibernation were sacrificed after 2-5 days of hibernation (continuous rectal temperature of 4 ºC). BAT, subcutaneous, retroperitoneal and epididimal WAT (sWAT, rWAT and eWAT), skeletal muscle (musculus quadriceps) and liver were sampled. Parallel, in order to examine the mechanisms of metabolic regulation in the BAT specific for hibernation, comparative study with rats acclimated to low temperatures, was made.
Results show that, when hibernating animals are exposed to low temperature, the cellular metabolism in all examined tissues/organs is initially subordinated to maintaining
euthermia, i.e. thermogenic process. In the early period of the cold-exposure, shivering and nonshivering thermogenesis is induced in the muscle and BAT, respectively. Although these processes are metabolically supported by the breakdown of glucose, the production of heat in both thermogenic organs is associated with energy imbalance. This is likely responsible for suppression of energy consumption pathways (primarly thermogenesis) during the extended acclimation period, and for preparation of ground squirrel to a state of hypothermia/hypometabolism. In the early period of acclimation, the fuel for thermogenesis is preferentially provided from visceral WAT depots (particularly eWAT), wherein decreased adipocyte surface profile, a result of intensive lipolysis, is observed. Later, during exposure to cold, when the thermogenic capacity in BAT is suppressed, activity of AMP-activated protein kinase is induced in all three WAT depots, lipolysis and energy-consuming pathways are "blocked" and oxidative metabolism is stimulated. Liver is central coordinator of the lipid and carbohydrate metabolism during cold acclimation.
In the deep hibernation, thermogenic capacity of BAT and skeletal muscle is significantly suppressed. It seems that hypoxia-inducible factor-1 (HIF-1) plays a central role in the metabolic remodeling of the thermogenic organs in hibernation, by both suppressing the energy-demanding, thermogenic processes, and also, by inducing glycolytic pathway, an important component of energy homeostasis in hypometabolic conditions. Similar metabolic reprogramming occurs in the visceral WAT depots. In hibernation, liver shows analogous metabolic strategy as in fasting conditions: induction of lipid catabolism and suppression of glucose degradation, with the simultaneous induction of gluconeogenesis.
Results indicate that capacity for lipid oxidation is increased in all tested tissues/organs, except in visceral WAT depots, during hibernation. In BAT, the intensification of fatty acid oxidation pathways primarily serves to maintain the necessary level of thermogenesis, whereas in skeletal muscle and liver this is associated with adaptation to hypothermic/hypometabolic conditions of hibernation. Noticeable lower level of interorgan communication, when it comes to lipid metabolism, suggests that tissues establish a certain degree of autonomy during hibernation.
In general, it can be concluded that characteristic tissue-dependent remodeling of the energy metabolism is the central axis and the precause of physiological plasticity of hibernators that provides them many advantages over the nonhibernating counterparts, and
the survival under adverse environmental conditions, whether they are active and euthermic or lethargic and hypothermic.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Molekulski mehanizmi metaboličke regulacije u hibernaciji i tokom aklimacije na hladnoću kod tekunice (Spermophilus citellus)
T1  - Molecular mechanisms of metabolic regulation in hibernation and during cold-acclimation in European ground squirrel (Spermophilus citellus)
SP  - 1
EP  - 191
UR  - https://hdl.handle.net/21.15107/rcub_nardus_2163
ER  - 

@phdthesis{
author = "Vučetić, Milica M.",
year = "2014",
abstract = "Fenomen hibernacije predstavlja fascinantan primer plastičnosti kod sisara. Hibernirajući sisari podliježu složenom nizu biohemijskih, fizioloških i bihevioralnih promjena u odgovoru na senzonske energetski-zahtijevne periode kuplovane sa redukovanom dopstupnošću hrane. Cilj disertacije je da se ispitaju promjene ćelijskog metabolizma u tkivima i organima tekunica, ključnim za održanje ukupne energetske homeostaze - mrko i bijelo masno tkivo (engl. brown adipose tissue, BAT i white adipose tissue, WAT), mišići i jetra, tokom perioda aklimacije na nisku temperaturu, kao i u fazi hibernacije.
Efekat aklimacije/hibernacije na metaboličko remodeliranje u tkivima i organima tekunica praćen je određivanjem: mitohondrijalnog kapaciteta (genska i/ili proteinska ekspresije komponenti respiratornog lanca i ATP sintaze); termogenog kapaciteta (ekspresija dekuplujućeg proteina 1); ekspresionih profila enzima ključnih metaboličkih puteva: glikolize, β-oksidacije, Krebsovog ciklusa, metabolizama triacilglicerola i glikogena. Ispitivani su i transkripcioni faktori uključeni u metaboličku regulaciju, kao i enzimi antioksidativne odbrane. Takođe, ispitivane su promjene u BAT i depoima WAT na strukturnom i ultrastrukturnom nivou.
Mužjaci evropske tekunice Spermophilus citellus su početkom septembra podijeljeni u dvije grupe: kontrolnu, koja je boravila na sobnoj temeraturi (22 ± 1 ºC) i grupu aklimiranu na nisku temperaturu (4 ± 1 ºC). Aktivne, eutermične tekunice, koje nisu ušle u duboku hibernaciju tokom aklimacije, žrtvovane su nakon 1, 3, 7, 12, odnosno 21 dan. Tekunice koje su ušle u hibernaciju žrtvovane su nakon 2-5 dana trajanja hibernacije (kontinuirana rektalna temperatura 4 ºC). BAT, subkutano, retroperitonealno i epididimalno WAT (sWAT, rWAT i eWAT), skeletni mišić (musculus quadriceps) i jetra su uzorkovani odmah po žrtvovanju. Kako bi se ispitali mehanizmi metaboličke regulacije u BAT, specifični za hibernatore, paralelno je rađena komparativna studija aklimacije pacova na nisku temperaturu.
Rezultati pokazuju da je, prilikom izlaganja hibernirajućih životinja niskoj temperaturi, ćelijski metabolizam u svim ispitivanim tkivima/organima inicijalno podređen održanju eutermije, tj. termogenom procesu koji se odvija u skeletnim mišićima i BAT. U ranom periodu izlaganja hladnoći, u skeletnim mišićima i BAT, dolazi do indukcije termogeneze (drhteće i nedrhteće), koja je metabolički podržana razlaganjem šećera. Međutim, produkcija toplote u oba termogena organa asocirana je sa energetskim disbalansom, koji je tokom produžene aklimacije najvjerovatnije odgovoran za supresiju puteva potrošnje energije (primarno termogeneze) i pripremu tekunica za ulazak u stanje hipotermije/hipometabolizma. Najveći dio goriva za termogenezu, u ranoj fazi aklimacije, obezbijeđuje se iz visceralnih depoa WAT (posebno eWAT), u kojima je detektovano smanjenje površine adipocitnog profila, usled intenzivne lipolize. Kasnije tokom izlaganja hladnoći, kada se termogeni kapacitet BAT suprimira, u sva tri ispitivana depoa WAT indukovana je aktivnost AMP-aktivirane protein kinase (AMPK), „blokirana” lipoliza i putevi potrošnje energije, a stimulisan oksidativni metabolizam. Jetra tokom aklimacije ima centralno mjesto koordinacije lipidnog i ugljenohidratnog metabolizma.
Rezultati disertacije pokazuju da je u fazi duboke hibernacije termogeni kapacitet BAT i skeletnih mišića značajno suprimiran. Takođe, hipoksija-inducibilni factor-1 (HIF-1) ima centralnu ulogu u metaboličkom remodeliranju termogenih organa u fazi hibernacije. Osim suprimiranja energetski-zahtijevnih termogenih procesa, HIF-1 u uslovima hipometabolizma ima ulogu i u regulaciji, tj. indukciji glikolitičkog puta, važne komponente energetske homeostaze tokom hibernacije. Slično reprogramiranje metabolizma dešava se i u visceralnim depoima WAT. Jetra u hibernaciji ostvaruje veoma sličnu metaboličku strategiju kao pri uslovima gladovanja: indukcija katabolizma lipida i supresija razlaganja glukoze, uz istovremenu indukciju glukoneogeneze.
Rezultati disertacije ukazuju da je u hibernaciji kapacitet za oksidaciju lipida povećan u svim ispitivanim tkivima/organima, osim u visceralnim depoima WAT. U BAT, intenziviranje puteva oksidacije masnih kiselina primarno služi održanju neophodnog nivoa termogeneze, dok je u skeletnim mišićima i jetri povezano sa adaptacijom na hipotermične/hipometaboličke uslove hibernacije. Uočljuv manji stepen interorganske komunikacije kada je lipidni metabolizam u pitanju, sugeriše da se tokom hibernacije uspostavlja određeni stepen tkivne autonomnosti.
Generalno se može zaključiti da karakteristično tkivno-zavisno remodelovanje energetskog metabolizma predstavlja centralnu osovinu i uslov fiziološke plastičnosti
hibernatora koja im omogućava brojne prednosti u odnosu na nehibernirajuće srodnike i preživljavanje u nepovoljnim uslovima sredine, bilo da su aktivni i eutermični ili letargični i hipotemični., The phenomenon of hibernation is a fascinating example of plasticity in mammals. Hibernating mammals are subjected to a complex series of biochemical, physiological and behavioral changes in response to seasonal energy-demanding periods coupled with reduced food availability. The aim of the thesis was to investigate metabolic changes in the key tissues and organs of the ground squirrel, responsible for maintaining overall energy homeostasis - brown and white adipose tissue (BAT and WAT), skeletal muscle and liver, during the acclimation to low temperature, as well as in the hibernation.
Effects of acclimation/hibernation on metabolic remodeling in the tissues and organs of the ground squirrel were determined by: mitochondrial capacity (gene and/or protein expression of the components of the respiratory chain and ATP synthase); thermogenic capacity (uncoupling protein 1 content), the expression profile of the key metabolic enzymes involved in: glycolysis, β-oxidation, Krebs cycle, glycogen and triglycerides metabolism. Furthermore, transcription factors involved in the metabolic regulation, as well as antioxidant enzymes, were examined. In parallel, we examined the changes in BAT and WAT depots on the structural and ultrastructural level.
Males of the European ground squirrel Spermophilus citellus were divided into two groups in early September: the control group, kept at room temperature (22 ± 1 º C) and a group acclimated to low temperature (4 ± 1 ºC). Active, euthermic ground squirrels, which did not enter into deep hibernation during acclimation, were sacrificed after 1, 3, 7, 12, or 21 days. Ground squirrels that entered hibernation were sacrificed after 2-5 days of hibernation (continuous rectal temperature of 4 ºC). BAT, subcutaneous, retroperitoneal and epididimal WAT (sWAT, rWAT and eWAT), skeletal muscle (musculus quadriceps) and liver were sampled. Parallel, in order to examine the mechanisms of metabolic regulation in the BAT specific for hibernation, comparative study with rats acclimated to low temperatures, was made.
Results show that, when hibernating animals are exposed to low temperature, the cellular metabolism in all examined tissues/organs is initially subordinated to maintaining
euthermia, i.e. thermogenic process. In the early period of the cold-exposure, shivering and nonshivering thermogenesis is induced in the muscle and BAT, respectively. Although these processes are metabolically supported by the breakdown of glucose, the production of heat in both thermogenic organs is associated with energy imbalance. This is likely responsible for suppression of energy consumption pathways (primarly thermogenesis) during the extended acclimation period, and for preparation of ground squirrel to a state of hypothermia/hypometabolism. In the early period of acclimation, the fuel for thermogenesis is preferentially provided from visceral WAT depots (particularly eWAT), wherein decreased adipocyte surface profile, a result of intensive lipolysis, is observed. Later, during exposure to cold, when the thermogenic capacity in BAT is suppressed, activity of AMP-activated protein kinase is induced in all three WAT depots, lipolysis and energy-consuming pathways are "blocked" and oxidative metabolism is stimulated. Liver is central coordinator of the lipid and carbohydrate metabolism during cold acclimation.
In the deep hibernation, thermogenic capacity of BAT and skeletal muscle is significantly suppressed. It seems that hypoxia-inducible factor-1 (HIF-1) plays a central role in the metabolic remodeling of the thermogenic organs in hibernation, by both suppressing the energy-demanding, thermogenic processes, and also, by inducing glycolytic pathway, an important component of energy homeostasis in hypometabolic conditions. Similar metabolic reprogramming occurs in the visceral WAT depots. In hibernation, liver shows analogous metabolic strategy as in fasting conditions: induction of lipid catabolism and suppression of glucose degradation, with the simultaneous induction of gluconeogenesis.
Results indicate that capacity for lipid oxidation is increased in all tested tissues/organs, except in visceral WAT depots, during hibernation. In BAT, the intensification of fatty acid oxidation pathways primarily serves to maintain the necessary level of thermogenesis, whereas in skeletal muscle and liver this is associated with adaptation to hypothermic/hypometabolic conditions of hibernation. Noticeable lower level of interorgan communication, when it comes to lipid metabolism, suggests that tissues establish a certain degree of autonomy during hibernation.
In general, it can be concluded that characteristic tissue-dependent remodeling of the energy metabolism is the central axis and the precause of physiological plasticity of hibernators that provides them many advantages over the nonhibernating counterparts, and
the survival under adverse environmental conditions, whether they are active and euthermic or lethargic and hypothermic.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Molekulski mehanizmi metaboličke regulacije u hibernaciji i tokom aklimacije na hladnoću kod tekunice (Spermophilus citellus), Molecular mechanisms of metabolic regulation in hibernation and during cold-acclimation in European ground squirrel (Spermophilus citellus)",
pages = "1-191",
url = "https://hdl.handle.net/21.15107/rcub_nardus_2163"
}

Vučetić, M. M.. (2014). Molekulski mehanizmi metaboličke regulacije u hibernaciji i tokom aklimacije na hladnoću kod tekunice (Spermophilus citellus). in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-191.
https://hdl.handle.net/21.15107/rcub_nardus_2163

Vučetić MM. Molekulski mehanizmi metaboličke regulacije u hibernaciji i tokom aklimacije na hladnoću kod tekunice (Spermophilus citellus). in University of Belgrade, Faculty of Biology. 2014;:1-191.
https://hdl.handle.net/21.15107/rcub_nardus_2163 .

Vučetić, Milica M., "Molekulski mehanizmi metaboličke regulacije u hibernaciji i tokom aklimacije na hladnoću kod tekunice (Spermophilus citellus)" in University of Belgrade, Faculty of Biology (2014):1-191,
https://hdl.handle.net/21.15107/rcub_nardus_2163 .