TY  - CONF
AU  - Mićić, Bojana
AU  - Veličković, Nataša
AU  - Đorđević, Ana
AU  - Teofilović, Ana
AU  - Kovačević, Sanja
AU  - Radovanović, Marina
AU  - Brkljačić, Jelena
AU  - Macut Djuro
AU  - Vojnović Milutinović, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6418
AB  - Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women’s
fertility and metabolic health throughout their life time. Insulin resistance and obesity, in conjunction
with excess androgens, are undeniably involved in its development. We aimed to elucidate how hyperandrogenemia
and prepubertal adiposity contribute to the development of metabolic disturbances in
rat model of PCOS.
Methods: The animal model of PCOS induced by 5a-dihydrotestosterone (DHT) was additionally challenged
by litter size reduction (LSR) during suckling period, to ensure overfeeding and development of
prepubertal adiposity. Systemic parameters of insulin sensitivity, along with markers of energy sensing,
insulin signaling, and lipid metabolism were analyzed in visceral adipose tissue (VAT) and skeletal muscle.
Results: The combination of treatments led to hyperinsulinemia and impaired systemic insulin sensitivity.
This was not accompanied with altered insulin signaling in the VAT, in spite of observed adipocytes
hypertrophy probably due to activation of AMPK and restrained lipogenesis in this tissue. On the other
hand, insulin signaling in skeletal muscle was impaired, which resulted in increased muscle fatty acid
uptake and oxidation after combined treatment. The switch to fatty acids oxidation subsequently led to
oxidative stress and inflammation, which was followed by adaptive activation of AMPK and increased
expression of its targets involved in antioxidant protection and mitochondrial biogenesis.
Conclusion: Our results suggest that prepubertal weight gain predisposes to insulin resistance development
in androgen-excess PCOS. The protective activation of AMPK in VAT and muscle makes it a potential
therapeutic target for insulin-resistant PCOS patients.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding
SP  - 144
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6418
ER  - 

@conference{
author = "Mićić, Bojana and Veličković, Nataša and Đorđević, Ana and Teofilović, Ana and Kovačević, Sanja and Radovanović, Marina and Brkljačić, Jelena and Macut Djuro and Vojnović Milutinović, Danijela",
year = "2023",
abstract = "Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women’s
fertility and metabolic health throughout their life time. Insulin resistance and obesity, in conjunction
with excess androgens, are undeniably involved in its development. We aimed to elucidate how hyperandrogenemia
and prepubertal adiposity contribute to the development of metabolic disturbances in
rat model of PCOS.
Methods: The animal model of PCOS induced by 5a-dihydrotestosterone (DHT) was additionally challenged
by litter size reduction (LSR) during suckling period, to ensure overfeeding and development of
prepubertal adiposity. Systemic parameters of insulin sensitivity, along with markers of energy sensing,
insulin signaling, and lipid metabolism were analyzed in visceral adipose tissue (VAT) and skeletal muscle.
Results: The combination of treatments led to hyperinsulinemia and impaired systemic insulin sensitivity.
This was not accompanied with altered insulin signaling in the VAT, in spite of observed adipocytes
hypertrophy probably due to activation of AMPK and restrained lipogenesis in this tissue. On the other
hand, insulin signaling in skeletal muscle was impaired, which resulted in increased muscle fatty acid
uptake and oxidation after combined treatment. The switch to fatty acids oxidation subsequently led to
oxidative stress and inflammation, which was followed by adaptive activation of AMPK and increased
expression of its targets involved in antioxidant protection and mitochondrial biogenesis.
Conclusion: Our results suggest that prepubertal weight gain predisposes to insulin resistance development
in androgen-excess PCOS. The protective activation of AMPK in VAT and muscle makes it a potential
therapeutic target for insulin-resistant PCOS patients.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding",
pages = "144",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6418"
}

Mićić, B., Veličković, N., Đorđević, A., Teofilović, A., Kovačević, S., Radovanović, M., Brkljačić, J., Macut Djuro,& Vojnović Milutinović, D.. (2023). Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 144.
https://hdl.handle.net/21.15107/rcub_ibiss_6418

Mićić B, Veličković N, Đorđević A, Teofilović A, Kovačević S, Radovanović M, Brkljačić J, Macut Djuro, Vojnović Milutinović D. Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:144.
https://hdl.handle.net/21.15107/rcub_ibiss_6418 .

Mićić, Bojana, Veličković, Nataša, Đorđević, Ana, Teofilović, Ana, Kovačević, Sanja, Radovanović, Marina, Brkljačić, Jelena, Macut Djuro, Vojnović Milutinović, Danijela, "Metabolic disturbances in animal model of polycystic ovary syndrome: impact of early postnatal overfeeding" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):144,
https://hdl.handle.net/21.15107/rcub_ibiss_6418 .

TY  - JOUR
AU  - Mićić, Bojana
AU  - Đorđević, Ana
AU  - Veličković, Nataša
AU  - Kovačević, Sanja
AU  - Martić, Teodora
AU  - Macut, Đuro
AU  - Vojnović-Milutinović, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5785
AB  - Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive
age, often associated with obesity and insulin resistance. Childhood obesity is an important
predisposing factor for the development of PCOS later in life. Being particularly interested in the
interplay between prepubertal obesity and hyperandrogenemia, we investigated the effects of early
postnatal overfeeding, accomplished by reducing litter size during the period of suckling, on energy
sensing and insulin signaling pathways in the gastrocnemius muscle of a rat model of PCOS-induced
by 5 -dihydrotestosterone (DHT). The combination of overfeeding and DHT treatment caused hyperinsulinemia
and decreased systemic insulin sensitivity. Early postnatal overfeeding induced defects
at critical nodes of the insulin signaling pathway in skeletal muscle, which was associated with
reduced glucose uptake in the presence of hyperandrogenemia. In this setting, under a combination
of overfeeding and DHT treatment, skeletal muscle switched to mitochondrial  -oxidation of fatty
acids, resulting in oxidative stress and inflammation that stimulated AMP-activated protein kinase
(AMPK) activity and its downstream targets involved in mitochondrial biogenesis and antioxidant
protection. Overall, a combination of overfeeding and hyperandrogenemia resulted in a prooxidative
and insulin-resistant state in skeletal muscle. This was accompanied by the activation of AMPK,
which could represent a potential therapeutic target in insulin-resistant PCOS patients.
PB  - Basel: MDPI
T2  - Biomedicines
T1  - AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding
IS  - 6
VL  - 11
DO  - 10.3390/biomedicines11061586
SP  - 1586
ER  - 

@article{
author = "Mićić, Bojana and Đorđević, Ana and Veličković, Nataša and Kovačević, Sanja and Martić, Teodora and Macut, Đuro and Vojnović-Milutinović, Danijela",
year = "2023",
abstract = "Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive
age, often associated with obesity and insulin resistance. Childhood obesity is an important
predisposing factor for the development of PCOS later in life. Being particularly interested in the
interplay between prepubertal obesity and hyperandrogenemia, we investigated the effects of early
postnatal overfeeding, accomplished by reducing litter size during the period of suckling, on energy
sensing and insulin signaling pathways in the gastrocnemius muscle of a rat model of PCOS-induced
by 5 -dihydrotestosterone (DHT). The combination of overfeeding and DHT treatment caused hyperinsulinemia
and decreased systemic insulin sensitivity. Early postnatal overfeeding induced defects
at critical nodes of the insulin signaling pathway in skeletal muscle, which was associated with
reduced glucose uptake in the presence of hyperandrogenemia. In this setting, under a combination
of overfeeding and DHT treatment, skeletal muscle switched to mitochondrial  -oxidation of fatty
acids, resulting in oxidative stress and inflammation that stimulated AMP-activated protein kinase
(AMPK) activity and its downstream targets involved in mitochondrial biogenesis and antioxidant
protection. Overall, a combination of overfeeding and hyperandrogenemia resulted in a prooxidative
and insulin-resistant state in skeletal muscle. This was accompanied by the activation of AMPK,
which could represent a potential therapeutic target in insulin-resistant PCOS patients.",
publisher = "Basel: MDPI",
journal = "Biomedicines",
title = "AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding",
number = "6",
volume = "11",
doi = "10.3390/biomedicines11061586",
pages = "1586"
}

Mićić, B., Đorđević, A., Veličković, N., Kovačević, S., Martić, T., Macut, Đ.,& Vojnović-Milutinović, D.. (2023). AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding. in Biomedicines
Basel: MDPI., 11(6), 1586.
https://doi.org/10.3390/biomedicines11061586

Mićić B, Đorđević A, Veličković N, Kovačević S, Martić T, Macut Đ, Vojnović-Milutinović D. AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding. in Biomedicines. 2023;11(6):1586.
doi:10.3390/biomedicines11061586 .

Mićić, Bojana, Đorđević, Ana, Veličković, Nataša, Kovačević, Sanja, Martić, Teodora, Macut, Đuro, Vojnović-Milutinović, Danijela, "AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding" in Biomedicines, 11, no. 6 (2023):1586,
https://doi.org/10.3390/biomedicines11061586 . .

TY  - JOUR
AU  - Jovanović, Mirna
AU  - Kovačević, Sanja
AU  - Brkljačić, Jelena
AU  - Đorđević, Ana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5756
AB  - Obesity is on the rise worldwide, and consequently, obesity-related non-communicable diseases are as well. Nutritional overload induces metabolic adaptations in an attempt to restore the disturbed balance, and the byproducts of the mechanisms at hand include an increased generation of reactive species. Obesity-related oxidative stress causes damage to vulnerable systems and ultimately contributes to neoplastic transformation. Dysfunctional obese adipose tissue releases cytokines and induces changes in the cell microenvironment, promoting cell survival and progression of the transformed cancer cells. Other than the increased risk of cancer development, obese cancer patients experience higher mortality rates and reduced therapy efficiency as well. The fact that obesity is considered the second leading preventable cause of cancer prioritizes the research on the mechanisms connecting obesity to cancerogenesis and finding the solutions to break the link. Oxidative stress is integral at different stages of cancer development and advancement in obese patients. Hypocaloric, balanced nutrition, and structured physical activity are some tools for relieving this burden. However, the sensitivity of simultaneously treating cancer and obesity poses a challenge. Further research on the obesity–cancer liaison would offer new perspectives on prevention programs and treatment development.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Oxidative Stress Linking Obesity and Cancer: Is Obesity a ‘Radical Trigger’ to Cancer?
IS  - 9
VL  - 24
DO  - 10.3390/ijms24098452
SP  - 8452
ER  - 

@article{
author = "Jovanović, Mirna and Kovačević, Sanja and Brkljačić, Jelena and Đorđević, Ana",
year = "2023",
abstract = "Obesity is on the rise worldwide, and consequently, obesity-related non-communicable diseases are as well. Nutritional overload induces metabolic adaptations in an attempt to restore the disturbed balance, and the byproducts of the mechanisms at hand include an increased generation of reactive species. Obesity-related oxidative stress causes damage to vulnerable systems and ultimately contributes to neoplastic transformation. Dysfunctional obese adipose tissue releases cytokines and induces changes in the cell microenvironment, promoting cell survival and progression of the transformed cancer cells. Other than the increased risk of cancer development, obese cancer patients experience higher mortality rates and reduced therapy efficiency as well. The fact that obesity is considered the second leading preventable cause of cancer prioritizes the research on the mechanisms connecting obesity to cancerogenesis and finding the solutions to break the link. Oxidative stress is integral at different stages of cancer development and advancement in obese patients. Hypocaloric, balanced nutrition, and structured physical activity are some tools for relieving this burden. However, the sensitivity of simultaneously treating cancer and obesity poses a challenge. Further research on the obesity–cancer liaison would offer new perspectives on prevention programs and treatment development.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Oxidative Stress Linking Obesity and Cancer: Is Obesity a ‘Radical Trigger’ to Cancer?",
number = "9",
volume = "24",
doi = "10.3390/ijms24098452",
pages = "8452"
}

Jovanović, M., Kovačević, S., Brkljačić, J.,& Đorđević, A.. (2023). Oxidative Stress Linking Obesity and Cancer: Is Obesity a ‘Radical Trigger’ to Cancer?. in International Journal of Molecular Sciences
Basel: MDPI., 24(9), 8452.
https://doi.org/10.3390/ijms24098452

Jovanović M, Kovačević S, Brkljačić J, Đorđević A. Oxidative Stress Linking Obesity and Cancer: Is Obesity a ‘Radical Trigger’ to Cancer?. in International Journal of Molecular Sciences. 2023;24(9):8452.
doi:10.3390/ijms24098452 .

Jovanović, Mirna, Kovačević, Sanja, Brkljačić, Jelena, Đorđević, Ana, "Oxidative Stress Linking Obesity and Cancer: Is Obesity a ‘Radical Trigger’ to Cancer?" in International Journal of Molecular Sciences, 24, no. 9 (2023):8452,
https://doi.org/10.3390/ijms24098452 . .

TY  - CONF
AU  - Brkljačić, Jelena
AU  - Veličković, Nataša
AU  - Vojnović-Milutinović, Danijela
AU  - Kovačević, Sanja
AU  - Teofilović, Ana
AU  - Bursać, Biljana
AU  - Pešić, Vesna
AU  - Đorđević, Ana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5710
AB  - Фруктоза је прост шећер одувек присутан у људској исхрани. До 20. века људи су
путем воћа и поврћа уносили релативно ниске количине фруктозе, да би током 20.
века, након увођења високофруктозног кукурузног сирупа у прехрамбену
индустрију, дневни унос фруктозе био учетворостручен што је коинцидирало са
растућом преваленцијом метаболичких поремећаја. Ипак, новије студије показују
да преваленција метаболичких поремећаја и даље расте иако је дневни унос шећера
стабилан или се чак смањује, што указује на допринос других фактора, као што су
смањена физичка активност и свакодневна изложеност стресу. Наша истраживања
на животињском моделу пацова који је храњен фруктозом и хронично излаган
комбинацији стресора пружају одговор на питање да ли, и у којим ситуацијама,
фруктоза може да смањује штетне ефекте стреса, а у којим условима стрес
потенцира штетне ефекте фруктозе? Резултати показују да фруктоза, стрес и
њихова комбинација, на ткивно и полно специфичан начин утичу на метаболизам
глукозе и липида, као и на редокс и инфламаторни статус у јетри, скелетним
мишићима и висцералном масном ткиву, а да поред метаболичких ефеката
фруктоза и стрес утичу и на понашање животиња. Будући да ефекти фруктозе
зависе од дозе и патофизиолошког стања организма, енергија која од ње потиче се
може ефикасно складиштити и по потреби користити кроз физичку активност, док
сталан повећан унос фруктозе, уз седентарни начин живота и стрес може
допринети развоју метаболичких и кардиоваскуларних обољења.
AB  - Fruktoza je prost šećer oduvek prisutan u ljudskoj ishrani. Do 20. veka ljudi su putem voća i povrća unosili relativno niske količine fruktoze, da bi tokom 20. veka, nakon uvođenja visokofruktoznog kukuruznog sirupa u prehrambenu industriju, dnevni unos fruktoze bio učetvorostručen što je koincidiralo sa rastućom prevalencijom metaboličkih poremećaja. Ipak, novije studije pokazuju da prevalencija metaboličkih poremećaja i dalje raste iako je dnevni unos šećera stabilan ili se čak smanjuje, što ukazuje na doprinos drugih faktora, kao što su smanjena fizička aktivnost i svakodnevna izloženost stresu. Naša istraživanja na životinjskom modelu pacova koji je hranjen fruktozom i hronično izlagan kombinaciji stresora pružaju odgovor na pitanje da li, i u kojim situacijama, fruktoza može da smanjuje štetne efekte stresa, a u kojim uslovima stres potencira štetne efekte fruktoze? Rezultati pokazuju da fruktoza, stres i njihova kombinacija, na tkivno i polno specifičan način utiču na metabolizam glukoze i lipida, kao i na redoks i inflamatorni status u jetri, skeletnim mišićima i visceralnom masnom tkivu, a da pored metaboličkih efekata fruktoza i stres utiču i na ponašanje životinja. Budući da efekti fruktoze zavise od doze i patofiziološkog stanja organizma, energija koja od nje potiče se može efikasno skladištiti i po potrebi koristiti kroz fizičku aktivnost, dok stalan povećan unos fruktoze, uz sedentarni način života i stres može doprineti razvoju metaboličkih i kardiovaskularnih oboljenja.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Fruktoza u ishrani: Ima li razloga za zabrinutost?
T1  - Фруктоза у исхрани: Има ли разлога за забринутост?
SP  - 284
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5710
ER  - 

@conference{
author = "Brkljačić, Jelena and Veličković, Nataša and Vojnović-Milutinović, Danijela and Kovačević, Sanja and Teofilović, Ana and Bursać, Biljana and Pešić, Vesna and Đorđević, Ana",
year = "2022",
abstract = "Фруктоза је прост шећер одувек присутан у људској исхрани. До 20. века људи су
путем воћа и поврћа уносили релативно ниске количине фруктозе, да би током 20.
века, након увођења високофруктозног кукурузног сирупа у прехрамбену
индустрију, дневни унос фруктозе био учетворостручен што је коинцидирало са
растућом преваленцијом метаболичких поремећаја. Ипак, новије студије показују
да преваленција метаболичких поремећаја и даље расте иако је дневни унос шећера
стабилан или се чак смањује, што указује на допринос других фактора, као што су
смањена физичка активност и свакодневна изложеност стресу. Наша истраживања
на животињском моделу пацова који је храњен фруктозом и хронично излаган
комбинацији стресора пружају одговор на питање да ли, и у којим ситуацијама,
фруктоза може да смањује штетне ефекте стреса, а у којим условима стрес
потенцира штетне ефекте фруктозе? Резултати показују да фруктоза, стрес и
њихова комбинација, на ткивно и полно специфичан начин утичу на метаболизам
глукозе и липида, као и на редокс и инфламаторни статус у јетри, скелетним
мишићима и висцералном масном ткиву, а да поред метаболичких ефеката
фруктоза и стрес утичу и на понашање животиња. Будући да ефекти фруктозе
зависе од дозе и патофизиолошког стања организма, енергија која од ње потиче се
може ефикасно складиштити и по потреби користити кроз физичку активност, док
сталан повећан унос фруктозе, уз седентарни начин живота и стрес може
допринети развоју метаболичких и кардиоваскуларних обољења., Fruktoza je prost šećer oduvek prisutan u ljudskoj ishrani. Do 20. veka ljudi su putem voća i povrća unosili relativno niske količine fruktoze, da bi tokom 20. veka, nakon uvođenja visokofruktoznog kukuruznog sirupa u prehrambenu industriju, dnevni unos fruktoze bio učetvorostručen što je koincidiralo sa rastućom prevalencijom metaboličkih poremećaja. Ipak, novije studije pokazuju da prevalencija metaboličkih poremećaja i dalje raste iako je dnevni unos šećera stabilan ili se čak smanjuje, što ukazuje na doprinos drugih faktora, kao što su smanjena fizička aktivnost i svakodnevna izloženost stresu. Naša istraživanja na životinjskom modelu pacova koji je hranjen fruktozom i hronično izlagan kombinaciji stresora pružaju odgovor na pitanje da li, i u kojim situacijama, fruktoza može da smanjuje štetne efekte stresa, a u kojim uslovima stres potencira štetne efekte fruktoze? Rezultati pokazuju da fruktoza, stres i njihova kombinacija, na tkivno i polno specifičan način utiču na metabolizam glukoze i lipida, kao i na redoks i inflamatorni status u jetri, skeletnim mišićima i visceralnom masnom tkivu, a da pored metaboličkih efekata fruktoza i stres utiču i na ponašanje životinja. Budući da efekti fruktoze zavise od doze i patofiziološkog stanja organizma, energija koja od nje potiče se može efikasno skladištiti i po potrebi koristiti kroz fizičku aktivnost, dok stalan povećan unos fruktoze, uz sedentarni način života i stres može doprineti razvoju metaboličkih i kardiovaskularnih oboljenja.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Fruktoza u ishrani: Ima li razloga za zabrinutost?, Фруктоза у исхрани: Има ли разлога за забринутост?",
pages = "284",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5710"
}

Brkljačić, J., Veličković, N., Vojnović-Milutinović, D., Kovačević, S., Teofilović, A., Bursać, B., Pešić, V.,& Đorđević, A.. (2022). Fruktoza u ishrani: Ima li razloga za zabrinutost?. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 284.
https://hdl.handle.net/21.15107/rcub_ibiss_5710

Brkljačić J, Veličković N, Vojnović-Milutinović D, Kovačević S, Teofilović A, Bursać B, Pešić V, Đorđević A. Fruktoza u ishrani: Ima li razloga za zabrinutost?. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:284.
https://hdl.handle.net/21.15107/rcub_ibiss_5710 .

Brkljačić, Jelena, Veličković, Nataša, Vojnović-Milutinović, Danijela, Kovačević, Sanja, Teofilović, Ana, Bursać, Biljana, Pešić, Vesna, Đorđević, Ana, "Fruktoza u ishrani: Ima li razloga za zabrinutost?" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):284,
https://hdl.handle.net/21.15107/rcub_ibiss_5710 .

TY  - JOUR
AU  - Tasić, Danica
AU  - Opačić, Miloš
AU  - Kovačević, Sanja
AU  - Nikolić-Kokić, Aleksandra
AU  - Dimitrijević, Milena
AU  - Nikolić, Dušan
AU  - Vojnović-Milutinović, Danijela
AU  - Blagojević, Duško
AU  - Đorđević, Ana
AU  - Brkljačić, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5025
AB  - The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys
are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate
copper metabolism in a way that affects redox homeostasis, thus contributing to progression
of metabolic disturbances in the kidney. We determined protein level of copper transporters,
chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes
function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation
and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of
superoxide dismutase and decreased metallothionein level, while rendering the level of copper
importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi
network unaffected. Stress had no effect on renal copper metabolism. The activity and expression
of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose,
independently of stress, decreased renal copper level, and modulated renal copper metabolism
as to preserve vital cellular function including mitochondrial energy production and antioxidative
defense, at the expense of intracellular copper storage.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function
IS  - 16
VL  - 23
DO  - 10.3390/ijms23169023
SP  - 9023
ER  - 

@article{
author = "Tasić, Danica and Opačić, Miloš and Kovačević, Sanja and Nikolić-Kokić, Aleksandra and Dimitrijević, Milena and Nikolić, Dušan and Vojnović-Milutinović, Danijela and Blagojević, Duško and Đorđević, Ana and Brkljačić, Jelena",
year = "2022",
abstract = "The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys
are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate
copper metabolism in a way that affects redox homeostasis, thus contributing to progression
of metabolic disturbances in the kidney. We determined protein level of copper transporters,
chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes
function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation
and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of
superoxide dismutase and decreased metallothionein level, while rendering the level of copper
importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi
network unaffected. Stress had no effect on renal copper metabolism. The activity and expression
of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose,
independently of stress, decreased renal copper level, and modulated renal copper metabolism
as to preserve vital cellular function including mitochondrial energy production and antioxidative
defense, at the expense of intracellular copper storage.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function",
number = "16",
volume = "23",
doi = "10.3390/ijms23169023",
pages = "9023"
}

Tasić, D., Opačić, M., Kovačević, S., Nikolić-Kokić, A., Dimitrijević, M., Nikolić, D., Vojnović-Milutinović, D., Blagojević, D., Đorđević, A.,& Brkljačić, J.. (2022). Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function. in International Journal of Molecular Sciences
Basel: MDPI., 23(16), 9023.
https://doi.org/10.3390/ijms23169023

Tasić D, Opačić M, Kovačević S, Nikolić-Kokić A, Dimitrijević M, Nikolić D, Vojnović-Milutinović D, Blagojević D, Đorđević A, Brkljačić J. Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function. in International Journal of Molecular Sciences. 2022;23(16):9023.
doi:10.3390/ijms23169023 .

Tasić, Danica, Opačić, Miloš, Kovačević, Sanja, Nikolić-Kokić, Aleksandra, Dimitrijević, Milena, Nikolić, Dušan, Vojnović-Milutinović, Danijela, Blagojević, Duško, Đorđević, Ana, Brkljačić, Jelena, "Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function" in International Journal of Molecular Sciences, 23, no. 16 (2022):9023,
https://doi.org/10.3390/ijms23169023 . .

TY  - JOUR
AU  - Sirif, Zidane Abdulbaset
AU  - Kovačević, Sanja
AU  - Bursać, Biljana
AU  - Lakić, Iva
AU  - Veličković, Nataša
AU  - Jevđović, Tanja
AU  - Đorđević, Ana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5024
AB  - Appetite regulation in the hypothalamus is dependent on
hormonal signals from the periphery, such as insulin and
leptin, and can be modulated by both sugar-rich diet and
stress. Our aim was to explore the effects of 9-week feeding
with 20% fructose solution combined with 4-week
chronic unpredictable stress, on appetite-regulating neuropeptides
and modulatory role of leptin and insulin signalling
in the hypothalamus of male Wistar rats. Energy
intake, body mass and adiposity, as well as circulatory
leptin and insulin concentrations were assessed. Hypothalamic
insulin signalling was analysed at the level of glucose
transporters, as well as at the protein level and phosphorylation
of insulin receptor, insulin receptor supstrate-1, Akt
and ERK. Phosphorylation of AMP-activated protein kinase
(AMPK), level of protein tyrosine phosphatase 1B (PTP1B)
and expression of leptin receptor (ObRb) and suppressor of
cytokine signalling 3 (SOCS3) were also analysed, together
with the expression of orexigenic agouti-related protein
(AgRP) and anorexigenic proopiomelanocortin (POMC) neuropeptides.
The results revealed that stress decreased body
mass and adiposity, blood leptin level and expression of
ObRb, SOCS3 and POMC, while combination with fructose
diet led to marked increase of AgRP, associated with AMPK
phosphorylation despite increased plasma insulin. Reduced
Akt, enhanced ERK activity and elevated PTP1B were also
observed in the hypothalamus of these animals. In conclusion,
our results showed that joint effects of fructose diet
and stress are more deleterious than the separate ones,
since inappropriate appetite control in the hypothalamus
may provide a setting for the disturbed energy homeostasis
in the long run.
PB  - Warsaw: Polish Biochemical Society
T2  - Acta Biochimica Polonica
T1  - Combination of chronic stress with fructose diet increases AMPactivated protein kinase phosphorylation and affects agoutirelated protein and proopiomelanocortin expression in the hypothalamus of male Wistar rats
IS  - 6075
DO  - 10.18388/abp.2020_6075
ER  - 

@article{
author = "Sirif, Zidane Abdulbaset and Kovačević, Sanja and Bursać, Biljana and Lakić, Iva and Veličković, Nataša and Jevđović, Tanja and Đorđević, Ana",
year = "2022",
abstract = "Appetite regulation in the hypothalamus is dependent on
hormonal signals from the periphery, such as insulin and
leptin, and can be modulated by both sugar-rich diet and
stress. Our aim was to explore the effects of 9-week feeding
with 20% fructose solution combined with 4-week
chronic unpredictable stress, on appetite-regulating neuropeptides
and modulatory role of leptin and insulin signalling
in the hypothalamus of male Wistar rats. Energy
intake, body mass and adiposity, as well as circulatory
leptin and insulin concentrations were assessed. Hypothalamic
insulin signalling was analysed at the level of glucose
transporters, as well as at the protein level and phosphorylation
of insulin receptor, insulin receptor supstrate-1, Akt
and ERK. Phosphorylation of AMP-activated protein kinase
(AMPK), level of protein tyrosine phosphatase 1B (PTP1B)
and expression of leptin receptor (ObRb) and suppressor of
cytokine signalling 3 (SOCS3) were also analysed, together
with the expression of orexigenic agouti-related protein
(AgRP) and anorexigenic proopiomelanocortin (POMC) neuropeptides.
The results revealed that stress decreased body
mass and adiposity, blood leptin level and expression of
ObRb, SOCS3 and POMC, while combination with fructose
diet led to marked increase of AgRP, associated with AMPK
phosphorylation despite increased plasma insulin. Reduced
Akt, enhanced ERK activity and elevated PTP1B were also
observed in the hypothalamus of these animals. In conclusion,
our results showed that joint effects of fructose diet
and stress are more deleterious than the separate ones,
since inappropriate appetite control in the hypothalamus
may provide a setting for the disturbed energy homeostasis
in the long run.",
publisher = "Warsaw: Polish Biochemical Society",
journal = "Acta Biochimica Polonica",
title = "Combination of chronic stress with fructose diet increases AMPactivated protein kinase phosphorylation and affects agoutirelated protein and proopiomelanocortin expression in the hypothalamus of male Wistar rats",
number = "6075",
doi = "10.18388/abp.2020_6075"
}

Sirif, Z. A., Kovačević, S., Bursać, B., Lakić, I., Veličković, N., Jevđović, T.,& Đorđević, A.. (2022). Combination of chronic stress with fructose diet increases AMPactivated protein kinase phosphorylation and affects agoutirelated protein and proopiomelanocortin expression in the hypothalamus of male Wistar rats. in Acta Biochimica Polonica
Warsaw: Polish Biochemical Society.(6075).
https://doi.org/10.18388/abp.2020_6075

Sirif ZA, Kovačević S, Bursać B, Lakić I, Veličković N, Jevđović T, Đorđević A. Combination of chronic stress with fructose diet increases AMPactivated protein kinase phosphorylation and affects agoutirelated protein and proopiomelanocortin expression in the hypothalamus of male Wistar rats. in Acta Biochimica Polonica. 2022;(6075).
doi:10.18388/abp.2020_6075 .

Sirif, Zidane Abdulbaset, Kovačević, Sanja, Bursać, Biljana, Lakić, Iva, Veličković, Nataša, Jevđović, Tanja, Đorđević, Ana, "Combination of chronic stress with fructose diet increases AMPactivated protein kinase phosphorylation and affects agoutirelated protein and proopiomelanocortin expression in the hypothalamus of male Wistar rats" in Acta Biochimica Polonica, no. 6075 (2022),
https://doi.org/10.18388/abp.2020_6075 . .

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

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

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

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

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

TY  - JOUR
AU  - Shirif, Abdulbaset Zidane
AU  - Kovačević, Sanja
AU  - Brkljačić, Jelena
AU  - Teofilović, Ana
AU  - Elaković, Ivana
AU  - Đorđević, Ana
AU  - Matić, Gordana
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4259
AB  - The modern lifestyle brings both excessive fructose consumption and daily exposure
to stress which could lead to metabolic disturbances and type 2 diabetes. Muscles are important
points of glucose and lipid metabolism, with a crucial role in the maintenance of systemic energy
homeostasis. We investigated whether 9-week fructose-enriched diet, with and without exposure to 4-
week unpredictable stress, disturbs insulin signaling in the skeletal muscle of male rats and evaluated
potential contributory roles of muscle lipid metabolism, glucocorticoid signaling and inflammation.
The combination of fructose-enriched diet and stress increased peroxisome proliferator-activated
receptors-  and -  and stimulated lipid uptake, lipolysis and  -oxidation in the muscle of fructosefed
stressed rats. Combination of treatment also decreased systemic insulin sensitivity judged by
lower R-QUICKI, and lowered muscle protein content and stimulatory phosphorylations of insulin
receptor supstrate-1 and Akt, as well as the level of 11 -hydroxysteroid dehydrogenase type 1
and glucocorticoid receptor. At the same time, increased levels of protein tyrosine phosphatase-1B,
nuclear factor- B, tumor necrosis factor- , were observed in the muscle of fructose-fed stressed rats.
Based on these results, we propose that decreased glucocorticoid signaling in the skeletal muscle
can make a setting for lipid-induced inflammation and the development of insulin resistance in
fructose-fed stressed rats.
PB  - Basel, Switzerland: MDPI
T2  - International Journal of Molecular Sciences, Special Issue Glucocorticoids and Metabolic Disorders
T1  - Decreased Glucocorticoid Signaling Potentiates Lipid-Induced Inflammation and Contributes to Insulin Resistance in the Skeletal Muscle of Fructose-Fed Male Rats Exposed to Stress
IS  - 13
VL  - 22
DO  - 10.3390/ijms22137206
SP  - 7206
ER  - 

@article{
author = "Shirif, Abdulbaset Zidane and Kovačević, Sanja and Brkljačić, Jelena and Teofilović, Ana and Elaković, Ivana and Đorđević, Ana and Matić, Gordana",
year = "2021",
abstract = "The modern lifestyle brings both excessive fructose consumption and daily exposure
to stress which could lead to metabolic disturbances and type 2 diabetes. Muscles are important
points of glucose and lipid metabolism, with a crucial role in the maintenance of systemic energy
homeostasis. We investigated whether 9-week fructose-enriched diet, with and without exposure to 4-
week unpredictable stress, disturbs insulin signaling in the skeletal muscle of male rats and evaluated
potential contributory roles of muscle lipid metabolism, glucocorticoid signaling and inflammation.
The combination of fructose-enriched diet and stress increased peroxisome proliferator-activated
receptors-  and -  and stimulated lipid uptake, lipolysis and  -oxidation in the muscle of fructosefed
stressed rats. Combination of treatment also decreased systemic insulin sensitivity judged by
lower R-QUICKI, and lowered muscle protein content and stimulatory phosphorylations of insulin
receptor supstrate-1 and Akt, as well as the level of 11 -hydroxysteroid dehydrogenase type 1
and glucocorticoid receptor. At the same time, increased levels of protein tyrosine phosphatase-1B,
nuclear factor- B, tumor necrosis factor- , were observed in the muscle of fructose-fed stressed rats.
Based on these results, we propose that decreased glucocorticoid signaling in the skeletal muscle
can make a setting for lipid-induced inflammation and the development of insulin resistance in
fructose-fed stressed rats.",
publisher = "Basel, Switzerland: MDPI",
journal = "International Journal of Molecular Sciences, Special Issue Glucocorticoids and Metabolic Disorders",
title = "Decreased Glucocorticoid Signaling Potentiates Lipid-Induced Inflammation and Contributes to Insulin Resistance in the Skeletal Muscle of Fructose-Fed Male Rats Exposed to Stress",
number = "13",
volume = "22",
doi = "10.3390/ijms22137206",
pages = "7206"
}

Shirif, A. Z., Kovačević, S., Brkljačić, J., Teofilović, A., Elaković, I., Đorđević, A.,& Matić, G.. (2021). Decreased Glucocorticoid Signaling Potentiates Lipid-Induced Inflammation and Contributes to Insulin Resistance in the Skeletal Muscle of Fructose-Fed Male Rats Exposed to Stress. in International Journal of Molecular Sciences, Special Issue Glucocorticoids and Metabolic Disorders
Basel, Switzerland: MDPI., 22(13), 7206.
https://doi.org/10.3390/ijms22137206

Shirif AZ, Kovačević S, Brkljačić J, Teofilović A, Elaković I, Đorđević A, Matić G. Decreased Glucocorticoid Signaling Potentiates Lipid-Induced Inflammation and Contributes to Insulin Resistance in the Skeletal Muscle of Fructose-Fed Male Rats Exposed to Stress. in International Journal of Molecular Sciences, Special Issue Glucocorticoids and Metabolic Disorders. 2021;22(13):7206.
doi:10.3390/ijms22137206 .

Shirif, Abdulbaset Zidane, Kovačević, Sanja, Brkljačić, Jelena, Teofilović, Ana, Elaković, Ivana, Đorđević, Ana, Matić, Gordana, "Decreased Glucocorticoid Signaling Potentiates Lipid-Induced Inflammation and Contributes to Insulin Resistance in the Skeletal Muscle of Fructose-Fed Male Rats Exposed to Stress" in International Journal of Molecular Sciences, Special Issue Glucocorticoids and Metabolic Disorders, 22, no. 13 (2021):7206,
https://doi.org/10.3390/ijms22137206 . .

TY  - JOUR
AU  - Kovačević, Sanja
AU  - Elaković, Ivana
AU  - Vojnović-Milutinović, Danijela
AU  - Nikolić-Kokić, Aleksandra
AU  - Blagojević, Duško
AU  - Matić, Gordana
AU  - Tappy, Luc
AU  - Đorđević, Ana
AU  - Brkljačić, Jelena
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4468
AB  - Background: Both fructose consumption and chronic stress contribute to the development of metabolic disorders.
The consequences of such combination are not fully understood.
Objective: We investigated whether fructose supplementation and chronic stress synergistically disturb hepatic lipid
and glucose metabolism. The role of energy sensing, redox, and inflammatory status during development of metabolic
disturbances was investigated.
Methods: Female Wistar rats, aged 2.5 mo, were divided into 4 experimental groups: control (C) fed a standard diet
(commercial food and drinking water); fructose (F) fed the same food and 10% fructose solution; stress (S) fed the
standard diet and subjected to chronic unpredictable stress and, stress + fructose (SF) combining conditions F and
S as above. Stress included daily stressors: cold water forced swimming, physical restraint, cold room, wet bedding,
rocking, switching, or tilting cages. After 9 wk, hepatic enzymes and transcription factors involved in gluconeogenesis,
lipogenesis, fatty acid oxidation, antioxidative defence, energy sensing, and cytokines were assessed by qPCR, Western
blotting, and spectrophotometry and analyzed by 2-factor ANOVA.
Results: Fructose increased AMP-activated protein kinase (AMPK) phosphorylation (40%; P < 0.05) and the ratio of
inhibitory phosphorylation to total acetyl-CoA carboxylase (46%; P < 0.01), and decreased sterol regulatory element
binding protein 1c nuclear translocation by 30% (P < 0.05) in F and SF compared with C rats. Increased phosPck
(phoenolpyruvate carboxykinase) (85%) and G6pase (glucose-6-phosphatase) (55%) was observed in S rats (P < 0.05).
A 40% decrease in Apob (apolipoprotein B-100) and an increase in hepatic lipids (P < 0.05), together with a double
increase in TNF-α (P < 0.001), were observed in S rats, but without liver histopathological changes. These stress effects
on lipid accumulation and TNF-α were abolished in SF rats (P < 0.05).
Conclusions: Fructose does not enhance stress effects on hepatic lipid and glucose metabolism but attenuates its
effects on hepatic lipid accumulation and inflammation, suggesting that, in female rats, AMPK activation prevails over
stress-induced effects.
PB  - Oxford University Press on behalf of the American Society of Nutrition
T2  - The Journal of Nutrition
T1  - Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats
IS  - 12
VL  - 151
DO  - 10.1093/jn/nxab294
SP  - 3661
EP  - 3670
ER  - 

@article{
author = "Kovačević, Sanja and Elaković, Ivana and Vojnović-Milutinović, Danijela and Nikolić-Kokić, Aleksandra and Blagojević, Duško and Matić, Gordana and Tappy, Luc and Đorđević, Ana and Brkljačić, Jelena",
year = "2021",
abstract = "Background: Both fructose consumption and chronic stress contribute to the development of metabolic disorders.
The consequences of such combination are not fully understood.
Objective: We investigated whether fructose supplementation and chronic stress synergistically disturb hepatic lipid
and glucose metabolism. The role of energy sensing, redox, and inflammatory status during development of metabolic
disturbances was investigated.
Methods: Female Wistar rats, aged 2.5 mo, were divided into 4 experimental groups: control (C) fed a standard diet
(commercial food and drinking water); fructose (F) fed the same food and 10% fructose solution; stress (S) fed the
standard diet and subjected to chronic unpredictable stress and, stress + fructose (SF) combining conditions F and
S as above. Stress included daily stressors: cold water forced swimming, physical restraint, cold room, wet bedding,
rocking, switching, or tilting cages. After 9 wk, hepatic enzymes and transcription factors involved in gluconeogenesis,
lipogenesis, fatty acid oxidation, antioxidative defence, energy sensing, and cytokines were assessed by qPCR, Western
blotting, and spectrophotometry and analyzed by 2-factor ANOVA.
Results: Fructose increased AMP-activated protein kinase (AMPK) phosphorylation (40%; P < 0.05) and the ratio of
inhibitory phosphorylation to total acetyl-CoA carboxylase (46%; P < 0.01), and decreased sterol regulatory element
binding protein 1c nuclear translocation by 30% (P < 0.05) in F and SF compared with C rats. Increased phosPck
(phoenolpyruvate carboxykinase) (85%) and G6pase (glucose-6-phosphatase) (55%) was observed in S rats (P < 0.05).
A 40% decrease in Apob (apolipoprotein B-100) and an increase in hepatic lipids (P < 0.05), together with a double
increase in TNF-α (P < 0.001), were observed in S rats, but without liver histopathological changes. These stress effects
on lipid accumulation and TNF-α were abolished in SF rats (P < 0.05).
Conclusions: Fructose does not enhance stress effects on hepatic lipid and glucose metabolism but attenuates its
effects on hepatic lipid accumulation and inflammation, suggesting that, in female rats, AMPK activation prevails over
stress-induced effects.",
publisher = "Oxford University Press on behalf of the American Society of Nutrition",
journal = "The Journal of Nutrition",
title = "Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats",
number = "12",
volume = "151",
doi = "10.1093/jn/nxab294",
pages = "3661-3670"
}

Kovačević, S., Elaković, I., Vojnović-Milutinović, D., Nikolić-Kokić, A., Blagojević, D., Matić, G., Tappy, L., Đorđević, A.,& Brkljačić, J.. (2021). Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats. in The Journal of Nutrition
Oxford University Press on behalf of the American Society of Nutrition., 151(12), 3661-3670.
https://doi.org/10.1093/jn/nxab294

Kovačević S, Elaković I, Vojnović-Milutinović D, Nikolić-Kokić A, Blagojević D, Matić G, Tappy L, Đorđević A, Brkljačić J. Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats. in The Journal of Nutrition. 2021;151(12):3661-3670.
doi:10.1093/jn/nxab294 .

Kovačević, Sanja, Elaković, Ivana, Vojnović-Milutinović, Danijela, Nikolić-Kokić, Aleksandra, Blagojević, Duško, Matić, Gordana, Tappy, Luc, Đorđević, Ana, Brkljačić, Jelena, "Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats" in The Journal of Nutrition, 151, no. 12 (2021):3661-3670,
https://doi.org/10.1093/jn/nxab294 . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Elaković, Ivana
AU  - Kovačević, Sanja
AU  - Vojnović-Milutinović, Danijela
AU  - Nikolić-Kokić, Aleksandra
AU  - Glban, Alhadi M.
AU  - Spasić, Mihajlo
AU  - Tappy, Luc
AU  - Đorđević, Ana
AU  - Matić, Gordana
AU  - Brkljačić, Jelena
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3983
AB  - The effects of early-life fructose consumption on hepatic signaling pathways and their relation to the development of metabolic disorders in later life are not fully understood. To investigate whether fructose over consumption at a young age induces alterations in glucocorticoid signaling that  might  contribute  to  development  of  metabolic  disturbances,  we  analysed  glucocorticoid receptor hormone-binding parameters and expression of its target genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) and lipid metabolism (lipin-1),as well as redox and inflammatory status in the liver of female rats subjected to a fructose-rich diet immediately after weaning.  The fructose diet increased hepatic corticosterone concentration,11β-hydroxysteroid  dehydrogenase  type  1  level,   glucocorticoid  receptor  protein  level  and hormone-binding activity, as well as lipin-1 level. The expression of glucose-6-phosphatase was reduced  in  fructose-fed  rats,  while  phosphoenolpyruvate  carboxykinase  remained  unaltered.The  fructose-rich  diet  increased  the  level  of  fructose  transporter  GLUT2,  while  the  expression of  fructolytic  enzymes  fructokinase  and  aldolase  B  remained  unaltered.   The  diet  also  affected pro-inflammatory pathways, but had no effect on the antioxidant defence system.  In conclusion, a fructose-rich diet applied immediately after weaning promoted lipogenesis and enhanced hepatic glucocorticoid signaling, possibly to protect against inflammatory damage, but without an effect on gluconeogenesis and antioxidant enzymes. Yet, prolonged treatment might ultimately lead to more pronounced metabolic disturbances.
PB  - Basel, Switzerland : Multidisciplinary Digital Publishing Institute (MDPI)
T2  - Nutrients
T1  - Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats
IS  - 11
VL  - 12
DO  - 10.3390/nu12113470
SP  - 3470
ER  - 

@article{
author = "Elaković, Ivana and Kovačević, Sanja and Vojnović-Milutinović, Danijela and Nikolić-Kokić, Aleksandra and Glban, Alhadi M. and Spasić, Mihajlo and Tappy, Luc and Đorđević, Ana and Matić, Gordana and Brkljačić, Jelena",
year = "2020",
abstract = "The effects of early-life fructose consumption on hepatic signaling pathways and their relation to the development of metabolic disorders in later life are not fully understood. To investigate whether fructose over consumption at a young age induces alterations in glucocorticoid signaling that  might  contribute  to  development  of  metabolic  disturbances,  we  analysed  glucocorticoid receptor hormone-binding parameters and expression of its target genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) and lipid metabolism (lipin-1),as well as redox and inflammatory status in the liver of female rats subjected to a fructose-rich diet immediately after weaning.  The fructose diet increased hepatic corticosterone concentration,11β-hydroxysteroid  dehydrogenase  type  1  level,   glucocorticoid  receptor  protein  level  and hormone-binding activity, as well as lipin-1 level. The expression of glucose-6-phosphatase was reduced  in  fructose-fed  rats,  while  phosphoenolpyruvate  carboxykinase  remained  unaltered.The  fructose-rich  diet  increased  the  level  of  fructose  transporter  GLUT2,  while  the  expression of  fructolytic  enzymes  fructokinase  and  aldolase  B  remained  unaltered.   The  diet  also  affected pro-inflammatory pathways, but had no effect on the antioxidant defence system.  In conclusion, a fructose-rich diet applied immediately after weaning promoted lipogenesis and enhanced hepatic glucocorticoid signaling, possibly to protect against inflammatory damage, but without an effect on gluconeogenesis and antioxidant enzymes. Yet, prolonged treatment might ultimately lead to more pronounced metabolic disturbances.",
publisher = "Basel, Switzerland : Multidisciplinary Digital Publishing Institute (MDPI)",
journal = "Nutrients",
title = "Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats",
number = "11",
volume = "12",
doi = "10.3390/nu12113470",
pages = "3470"
}

Elaković, I., Kovačević, S., Vojnović-Milutinović, D., Nikolić-Kokić, A., Glban, A. M., Spasić, M., Tappy, L., Đorđević, A., Matić, G.,& Brkljačić, J.. (2020). Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats. in Nutrients
Basel, Switzerland : Multidisciplinary Digital Publishing Institute (MDPI)., 12(11), 3470.
https://doi.org/10.3390/nu12113470

Elaković I, Kovačević S, Vojnović-Milutinović D, Nikolić-Kokić A, Glban AM, Spasić M, Tappy L, Đorđević A, Matić G, Brkljačić J. Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats. in Nutrients. 2020;12(11):3470.
doi:10.3390/nu12113470 .

Elaković, Ivana, Kovačević, Sanja, Vojnović-Milutinović, Danijela, Nikolić-Kokić, Aleksandra, Glban, Alhadi M., Spasić, Mihajlo, Tappy, Luc, Đorđević, Ana, Matić, Gordana, Brkljačić, Jelena, "Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats" in Nutrients, 12, no. 11 (2020):3470,
https://doi.org/10.3390/nu12113470 . .

TY  - CONF
AU  - Radovanović, Marina
AU  - Kovačević, Sanja
AU  - Elaković, Ivana
AU  - Vojnović-Milutinović, Danijela
AU  - Matić, Gordana
AU  - Brkljačić, Jelena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5252
AB  - The effects of early-life fructose consumption and their relation to metabolic diseases risk
in adulthood are not yet elucidated. This study explored the direct effects of a diet regime
characterized by fructose enrichment on glucocorticoid receptor signaling in the liver of
female rats immediately after weaning. 21 day-old female Wistar rats were subjected to a 9
week-long diet regime involving standard chow in combination with either the 10%
fructose solution or tap water. Glucocorticoid receptor hormone binding parameters,
intracellular distribution of this molecule as well as the expression of its target genes
involved in lipid metabolism (most notably Lipin-1) and glucose metabolism (PEPCK),
were measured. An increase in the hepatic glucocorticoid receptor hormone binding
activity as well as an elevated nuclear translocation of the receptor, in concert with the
increased protein levels of Lipin-1 were observed after fructose enriched diet. This was
preceeded by a hepatic elevation in Glut-2 fructose transporter expression. Fructose-
enriched diet starting immediately after weaning enhanced hepatic glucocorticoid signaling
in young female rats and promoted lypogenesis as evidenced not only by the lipin-1
increase but also by FAS, ACC and SCREBP-1 expression elevations contributing to
hypertriglyceridemia and the expansion of the visceral adipose tissue 1, with no effect on
the hepatic gluconeogenesis. These results imply that while most parameters remained
within physiological reactivity, prolonged treatment might ultimately lead to more
pronounced metabolic disturbances.
PB  - Belgrade: Faculty of Chemistry
C3  - The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia
T1  - Fructose consumption affects glucocorticoid receptor signaling and increases lipogenesis in the liver of young female rats
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5252
ER  - 

@conference{
author = "Radovanović, Marina and Kovačević, Sanja and Elaković, Ivana and Vojnović-Milutinović, Danijela and Matić, Gordana and Brkljačić, Jelena",
year = "2019",
abstract = "The effects of early-life fructose consumption and their relation to metabolic diseases risk
in adulthood are not yet elucidated. This study explored the direct effects of a diet regime
characterized by fructose enrichment on glucocorticoid receptor signaling in the liver of
female rats immediately after weaning. 21 day-old female Wistar rats were subjected to a 9
week-long diet regime involving standard chow in combination with either the 10%
fructose solution or tap water. Glucocorticoid receptor hormone binding parameters,
intracellular distribution of this molecule as well as the expression of its target genes
involved in lipid metabolism (most notably Lipin-1) and glucose metabolism (PEPCK),
were measured. An increase in the hepatic glucocorticoid receptor hormone binding
activity as well as an elevated nuclear translocation of the receptor, in concert with the
increased protein levels of Lipin-1 were observed after fructose enriched diet. This was
preceeded by a hepatic elevation in Glut-2 fructose transporter expression. Fructose-
enriched diet starting immediately after weaning enhanced hepatic glucocorticoid signaling
in young female rats and promoted lypogenesis as evidenced not only by the lipin-1
increase but also by FAS, ACC and SCREBP-1 expression elevations contributing to
hypertriglyceridemia and the expansion of the visceral adipose tissue 1, with no effect on
the hepatic gluconeogenesis. These results imply that while most parameters remained
within physiological reactivity, prolonged treatment might ultimately lead to more
pronounced metabolic disturbances.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia",
title = "Fructose consumption affects glucocorticoid receptor signaling and increases lipogenesis in the liver of young female rats",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5252"
}

Radovanović, M., Kovačević, S., Elaković, I., Vojnović-Milutinović, D., Matić, G.,& Brkljačić, J.. (2019). Fructose consumption affects glucocorticoid receptor signaling and increases lipogenesis in the liver of young female rats. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia
Belgrade: Faculty of Chemistry..
https://hdl.handle.net/21.15107/rcub_ibiss_5252

Radovanović M, Kovačević S, Elaković I, Vojnović-Milutinović D, Matić G, Brkljačić J. Fructose consumption affects glucocorticoid receptor signaling and increases lipogenesis in the liver of young female rats. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia. 2019;.
https://hdl.handle.net/21.15107/rcub_ibiss_5252 .

Radovanović, Marina, Kovačević, Sanja, Elaković, Ivana, Vojnović-Milutinović, Danijela, Matić, Gordana, Brkljačić, Jelena, "Fructose consumption affects glucocorticoid receptor signaling and increases lipogenesis in the liver of young female rats" in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia (2019),
https://hdl.handle.net/21.15107/rcub_ibiss_5252 .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - CONF
AU  - Kovačević, Sanja
AU  - Đorđević, Ana
AU  - Matić, Gordana
AU  - Elaković, Ivana
PY  - 2019
UR  - https://www.faobmbkl2019.com/abstract-book
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3989
AB  - Modern diet, rich in refined sugars and sweeteners, led to dramatic increase in fructose intake especially in young population. Excessive fructose intake has been associated with growing rate of obesity, insulin resistance and development of metabolic syndrome, women being more prone than men. Chronic low-grade inflammation accompanies obesity and has been implicated in the pathogenesis of obesity-related disorders including metabolic syndrome and insulin resistance. To elucidate whether fructose overconsumption causes inflammation in the visceral adipose tissue (VAT) of young and adult female rats thus contributing to the development of obesity and insulin resistance. We investigated the effects of 9-week fructose-enriched diet applied immediately after weaning (young) or at the 2.5 months of age (adult) on nuclear factor κB (NF-κB) intracellular distribution, and on the expression of pro-inflammatory cytokines (IL-1β, IL-6 and TNFα) in female Wistar rats. Additionally, insulin signalling was analysed at the level of insulin receptor substrate-1 (IRS1), Akt kinase, and their activating and inhibitory phosphorylations. Fructose-enriched diet increased absolute and relative VAT mass in young female rats. There were no changes in VAT mass of adults after fructose diet, even though histological analysis revealed the presence of islets of smaller adipocytes, which indicated adipogenesis. Both young and adult female fructose-fed rats had increased nuclear accumulation of NF-κB and elevated expression of pro-inflammatory cytokines in the VAT. In adults, fructose overconsumption reduced protein content and stimulatory phosphorylation of Akt kinase, while increasing inhibitory phosphorylation of IRS-1. These changes were not observed in young female rats. The results suggest that fructose-enriched diet causes inflammation in VAT of both young and adult female rats. Our work supports the stand that VAT inflammation could represent one of the earliest metabolic perturbations upon fructose overconsumption, since it can occur even before the onset of obesity or insulin resistance. Additionally, only adults developed VAT insulin resistance, indicating age-dependent differences in insulin signalling system and its response to fructose overconsumption in female rats.
PB  - Malaysian Society for Biochemistry and Molecular Biology
PB  - Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB)
PB  - International Union of Biochemistry and Molecular Biology (IUBMB)
C3  - Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP)
T1  - Metabolic status of adipose tissue after fructose overconsumption – differences between young and adult female rats
SP  - 3
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3989
ER  - 

@conference{
author = "Kovačević, Sanja and Đorđević, Ana and Matić, Gordana and Elaković, Ivana",
year = "2019",
abstract = "Modern diet, rich in refined sugars and sweeteners, led to dramatic increase in fructose intake especially in young population. Excessive fructose intake has been associated with growing rate of obesity, insulin resistance and development of metabolic syndrome, women being more prone than men. Chronic low-grade inflammation accompanies obesity and has been implicated in the pathogenesis of obesity-related disorders including metabolic syndrome and insulin resistance. To elucidate whether fructose overconsumption causes inflammation in the visceral adipose tissue (VAT) of young and adult female rats thus contributing to the development of obesity and insulin resistance. We investigated the effects of 9-week fructose-enriched diet applied immediately after weaning (young) or at the 2.5 months of age (adult) on nuclear factor κB (NF-κB) intracellular distribution, and on the expression of pro-inflammatory cytokines (IL-1β, IL-6 and TNFα) in female Wistar rats. Additionally, insulin signalling was analysed at the level of insulin receptor substrate-1 (IRS1), Akt kinase, and their activating and inhibitory phosphorylations. Fructose-enriched diet increased absolute and relative VAT mass in young female rats. There were no changes in VAT mass of adults after fructose diet, even though histological analysis revealed the presence of islets of smaller adipocytes, which indicated adipogenesis. Both young and adult female fructose-fed rats had increased nuclear accumulation of NF-κB and elevated expression of pro-inflammatory cytokines in the VAT. In adults, fructose overconsumption reduced protein content and stimulatory phosphorylation of Akt kinase, while increasing inhibitory phosphorylation of IRS-1. These changes were not observed in young female rats. The results suggest that fructose-enriched diet causes inflammation in VAT of both young and adult female rats. Our work supports the stand that VAT inflammation could represent one of the earliest metabolic perturbations upon fructose overconsumption, since it can occur even before the onset of obesity or insulin resistance. Additionally, only adults developed VAT insulin resistance, indicating age-dependent differences in insulin signalling system and its response to fructose overconsumption in female rats.",
publisher = "Malaysian Society for Biochemistry and Molecular Biology, Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB), International Union of Biochemistry and Molecular Biology (IUBMB)",
journal = "Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP)",
title = "Metabolic status of adipose tissue after fructose overconsumption – differences between young and adult female rats",
pages = "3",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3989"
}

Kovačević, S., Đorđević, A., Matić, G.,& Elaković, I.. (2019). Metabolic status of adipose tissue after fructose overconsumption – differences between young and adult female rats. in Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP)
Malaysian Society for Biochemistry and Molecular Biology., 3.
https://hdl.handle.net/21.15107/rcub_ibiss_3989

Kovačević S, Đorđević A, Matić G, Elaković I. Metabolic status of adipose tissue after fructose overconsumption – differences between young and adult female rats. in Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP). 2019;:3.
https://hdl.handle.net/21.15107/rcub_ibiss_3989 .

Kovačević, Sanja, Đorđević, Ana, Matić, Gordana, Elaković, Ivana, "Metabolic status of adipose tissue after fructose overconsumption – differences between young and adult female rats" in Kuala Lumpur, Malaysia : 27th FAOBMB & 44th MSBMB Conference Young Scientist Program (YSP) (2019):3,
https://hdl.handle.net/21.15107/rcub_ibiss_3989 .

TY  - JOUR
AU  - Kovačević, Sanja
AU  - Brkljačić, Jelena
AU  - Matić, Gordana
AU  - Elaković, Ivana
PY  - 2019
UR  - http://www.ncbi.nlm.nih.gov/pubmed/30572328
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3387
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3404
AB  - BACKGROUND Increased fructose consumption and chronic exposure to stress have been associated with the development of obesity and insulin resistance. In the hypothalamus, a crossroad of stress responses and energy balance, insulin and glucocorticoids regulate the expression of orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), and anorexigenic neuropeptides, proopio-melanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). OBJECTIVES We investigated whether chronic stress and fructose diet disrupt these hormonal signaling pathways and appetite control in the hypothalamus, contributing to the development of insulin resistance and obesity. Potential roles of hypothalamic inflammation and oxidative stress in the development of insulin resistance were also analyzed. METHODS Insulin, glucocorticoid, and leptin signaling, expression of orexigenic and anorexigenic neuropeptides, and antioxidative and inflammatory statuses in the whole hypothalamus of fructose-fed female rats exposed to unpredictable stress for 9 weeks were analyzed using quantitative PCR and Western blotting. RESULTS Chronic stress combined with a fructose-enriched diet reduced protein content and stimulatory phosphorylation of Akt kinase, and elevated 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor expression, while alterations in appetite regulation (NPY, AgRP, POMC, CART, leptin receptor, and SOCS3 expression) were not observed. The expression of antioxidative defense enzymes (mitochondrial manganese superoxide dismutase 2, glutathione reductase, and catalase) and proinflammatory cytokines (IL-1β, IL-6, and TNFα) was reduced. CONCLUSIONS Our results underline the combination of long-term stress exposure and fructose overconsumption as more detrimental for hypothalamic function than for either of the factors separately, as it enhanced glucocorticoid and impaired insulin signaling, antioxidative -defense, and inflammatory responses of this homeostasis- regulating center.
T2  - Neuroendocrinology
T1  - Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats.
DO  - 10.1159/000496391
ER  - 

@article{
author = "Kovačević, Sanja and Brkljačić, Jelena and Matić, Gordana and Elaković, Ivana",
year = "2019",
abstract = "BACKGROUND Increased fructose consumption and chronic exposure to stress have been associated with the development of obesity and insulin resistance. In the hypothalamus, a crossroad of stress responses and energy balance, insulin and glucocorticoids regulate the expression of orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), and anorexigenic neuropeptides, proopio-melanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). OBJECTIVES We investigated whether chronic stress and fructose diet disrupt these hormonal signaling pathways and appetite control in the hypothalamus, contributing to the development of insulin resistance and obesity. Potential roles of hypothalamic inflammation and oxidative stress in the development of insulin resistance were also analyzed. METHODS Insulin, glucocorticoid, and leptin signaling, expression of orexigenic and anorexigenic neuropeptides, and antioxidative and inflammatory statuses in the whole hypothalamus of fructose-fed female rats exposed to unpredictable stress for 9 weeks were analyzed using quantitative PCR and Western blotting. RESULTS Chronic stress combined with a fructose-enriched diet reduced protein content and stimulatory phosphorylation of Akt kinase, and elevated 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor expression, while alterations in appetite regulation (NPY, AgRP, POMC, CART, leptin receptor, and SOCS3 expression) were not observed. The expression of antioxidative defense enzymes (mitochondrial manganese superoxide dismutase 2, glutathione reductase, and catalase) and proinflammatory cytokines (IL-1β, IL-6, and TNFα) was reduced. CONCLUSIONS Our results underline the combination of long-term stress exposure and fructose overconsumption as more detrimental for hypothalamic function than for either of the factors separately, as it enhanced glucocorticoid and impaired insulin signaling, antioxidative -defense, and inflammatory responses of this homeostasis- regulating center.",
journal = "Neuroendocrinology",
title = "Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats.",
doi = "10.1159/000496391"
}

Kovačević, S., Brkljačić, J., Matić, G.,& Elaković, I.. (2019). Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats.. in Neuroendocrinology.
https://doi.org/10.1159/000496391

Kovačević S, Brkljačić J, Matić G, Elaković I. Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats.. in Neuroendocrinology. 2019;.
doi:10.1159/000496391 .

Kovačević, Sanja, Brkljačić, Jelena, Matić, Gordana, Elaković, Ivana, "Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats." in Neuroendocrinology (2019),
https://doi.org/10.1159/000496391 . .

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

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

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

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

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

TY  - JOUR
AU  - Kovačević, Sanja
AU  - Brkljačić, Jelena
AU  - Matić, Gordana
AU  - Elaković, Ivana
PY  - 2019
UR  - http://www.ncbi.nlm.nih.gov/pubmed/30572328
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3387
AB  - BACKGROUND Increased fructose consumption and chronic exposure to stress have been associated with the development of obesity and insulin resistance. In the hypothalamus, a crossroad of stress responses and energy balance, insulin and glucocorticoids regulate the expression of orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), and anorexigenic neuropeptides, proopio-melanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). OBJECTIVES We investigated whether chronic stress and fructose diet disrupt these hormonal signaling pathways and appetite control in the hypothalamus, contributing to the development of insulin resistance and obesity. Potential roles of hypothalamic inflammation and oxidative stress in the development of insulin resistance were also analyzed. METHODS Insulin, glucocorticoid, and leptin signaling, expression of orexigenic and anorexigenic neuropeptides, and antioxidative and inflammatory statuses in the whole hypothalamus of fructose-fed female rats exposed to unpredictable stress for 9 weeks were analyzed using quantitative PCR and Western blotting. RESULTS Chronic stress combined with a fructose-enriched diet reduced protein content and stimulatory phosphorylation of Akt kinase, and elevated 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor expression, while alterations in appetite regulation (NPY, AgRP, POMC, CART, leptin receptor, and SOCS3 expression) were not observed. The expression of antioxidative defense enzymes (mitochondrial manganese superoxide dismutase 2, glutathione reductase, and catalase) and proinflammatory cytokines (IL-1β, IL-6, and TNFα) was reduced. CONCLUSIONS Our results underline the combination of long-term stress exposure and fructose overconsumption as more detrimental for hypothalamic function than for either of the factors separately, as it enhanced glucocorticoid and impaired insulin signaling, antioxidative -defense, and inflammatory responses of this homeostasis- regulating center.
T2  - Neuroendocrinology
T1  - Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats.
IS  - 4
VL  - 108
DO  - 10.1159/000496391
SP  - 278
EP  - 290
ER  - 

@article{
author = "Kovačević, Sanja and Brkljačić, Jelena and Matić, Gordana and Elaković, Ivana",
year = "2019",
abstract = "BACKGROUND Increased fructose consumption and chronic exposure to stress have been associated with the development of obesity and insulin resistance. In the hypothalamus, a crossroad of stress responses and energy balance, insulin and glucocorticoids regulate the expression of orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), and anorexigenic neuropeptides, proopio-melanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). OBJECTIVES We investigated whether chronic stress and fructose diet disrupt these hormonal signaling pathways and appetite control in the hypothalamus, contributing to the development of insulin resistance and obesity. Potential roles of hypothalamic inflammation and oxidative stress in the development of insulin resistance were also analyzed. METHODS Insulin, glucocorticoid, and leptin signaling, expression of orexigenic and anorexigenic neuropeptides, and antioxidative and inflammatory statuses in the whole hypothalamus of fructose-fed female rats exposed to unpredictable stress for 9 weeks were analyzed using quantitative PCR and Western blotting. RESULTS Chronic stress combined with a fructose-enriched diet reduced protein content and stimulatory phosphorylation of Akt kinase, and elevated 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor expression, while alterations in appetite regulation (NPY, AgRP, POMC, CART, leptin receptor, and SOCS3 expression) were not observed. The expression of antioxidative defense enzymes (mitochondrial manganese superoxide dismutase 2, glutathione reductase, and catalase) and proinflammatory cytokines (IL-1β, IL-6, and TNFα) was reduced. CONCLUSIONS Our results underline the combination of long-term stress exposure and fructose overconsumption as more detrimental for hypothalamic function than for either of the factors separately, as it enhanced glucocorticoid and impaired insulin signaling, antioxidative -defense, and inflammatory responses of this homeostasis- regulating center.",
journal = "Neuroendocrinology",
title = "Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats.",
number = "4",
volume = "108",
doi = "10.1159/000496391",
pages = "278-290"
}

Kovačević, S., Brkljačić, J., Matić, G.,& Elaković, I.. (2019). Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats.. in Neuroendocrinology, 108(4), 278-290.
https://doi.org/10.1159/000496391

Kovačević S, Brkljačić J, Matić G, Elaković I. Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats.. in Neuroendocrinology. 2019;108(4):278-290.
doi:10.1159/000496391 .

Kovačević, Sanja, Brkljačić, Jelena, Matić, Gordana, Elaković, Ivana, "Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats." in Neuroendocrinology, 108, no. 4 (2019):278-290,
https://doi.org/10.1159/000496391 . .

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

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

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

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

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

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

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

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

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

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