Swiss National Science Foundation, [Grant SCOPES JRP IZ73Z0_152331]

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Swiss National Science Foundation, [Grant SCOPES JRP IZ73Z0_152331]

Authors

Publications

Metabolic status of adipose tissue after fructose overconsumption – differences between young and adult female rats

Kovačević, Sanja; Đorđević, Ana; Matić, Gordana; Elaković, Ivana

(Malaysian Society for Biochemistry and Molecular Biology, 2019)

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 .

Combination Of Fructose And Stress Induces Insulin Resistance And Disturbs Lipid Metabolism In Muscle And Adipose Tissue Of Rats

Kovačević, Sanja; Bursać, Biljana; Đorđević, Ana; Gligorovska, Ljupka; Matić, Gordana; Elaković, Ivana

(EMBO Press, 2019)

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 .

Effects Of Fructose-enriched Diet On Inflammation And Insulin Signaling In The Hypothalamus And Visceral Adipose Tissue Of Female Rats

Đorđević, Ana; Kovačević, Sanja; Matić, Gordana; Elaković, Ivana

(Belgrade: Institute for Biological Research “Siniša Stanković”, 2018)

TY  - CONF
AU  - Kovačević, Sanja
AU  - Matić, Gordana
AU  - Elaković, Ivana
PY  - 2018
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3986
AB  - Introduction 
Increased fructose consumption, mainly through sweetened beverages, coincides with growing rate of obesity, women being more prone than men. Chronic low-grade inflammation has been implicated in the pathogenesis of obesity-related disorders including metabolic syndrome and insulin resistance.
The aim 
We investigated whether fructose overconsumption causes inflammation in the visceral adipose tissue (VAT) and hypothalamus of female rats contributing to development of obesity and insulin resistance.
Methods 
Using qPCR and Western blot, we examined the effects of 9-week fructose-enriched diet on inflammatory status, insulin and leptin signaling in the VAT and hypothalamus, as well as on the expression of orexigenic and anorexigenic neuropeptides in the hypothalamus.
Results 
Fructose-fed rats had increased nuclear accumulation of nuclear factor κB (NF-κB) and elevated expression of pro-inflammatory cytokines (IL-1β, IL6, and TNFα), as well as increased protein level of macrophage-specific marker F4/80 in the VAT. In the same tissue, fructose overconsumption reduced protein content and stimulatory phosphorylation of Akt kinase, while increasing inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1). There were no changes in VAT mass, nor in inflammatory markers, insulin and leptin signaling (leptin receptor and SOCS3 expression) and appetite regulation (NPY, AgRP, POMC and CART) in the hypothalamus.
Conclusions 
The results suggest that fructose overconsumption causes alterations in pro-inflammatory markers and reduces insulin signaling in the VAT of female rats. These alterations could be one of the first consequences of fructose overconsumption, since they were detected in the absence of obesity, and hypothalamic inflammation and insulin and leptin resistance.
PB  - Belgrade: Institute for Biological Research “Siniša Stanković”
C3  - Program & Book of Abstracts : IUBMB Advanced School Nutrition, Metabolism and Aging
T1  - Effects Of Fructose-enriched Diet On Inflammation And Insulin Signaling In The Hypothalamus And Visceral Adipose Tissue Of Female Rats
SP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3986
ER  - 
@conference{
editor = "Đorđević, Ana",
author = "Kovačević, Sanja and Matić, Gordana and Elaković, Ivana",
year = "2018",
abstract = "Introduction 
Increased fructose consumption, mainly through sweetened beverages, coincides with growing rate of obesity, women being more prone than men. Chronic low-grade inflammation has been implicated in the pathogenesis of obesity-related disorders including metabolic syndrome and insulin resistance.
The aim 
We investigated whether fructose overconsumption causes inflammation in the visceral adipose tissue (VAT) and hypothalamus of female rats contributing to development of obesity and insulin resistance.
Methods 
Using qPCR and Western blot, we examined the effects of 9-week fructose-enriched diet on inflammatory status, insulin and leptin signaling in the VAT and hypothalamus, as well as on the expression of orexigenic and anorexigenic neuropeptides in the hypothalamus.
Results 
Fructose-fed rats had increased nuclear accumulation of nuclear factor κB (NF-κB) and elevated expression of pro-inflammatory cytokines (IL-1β, IL6, and TNFα), as well as increased protein level of macrophage-specific marker F4/80 in the VAT. In the same tissue, fructose overconsumption reduced protein content and stimulatory phosphorylation of Akt kinase, while increasing inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1). There were no changes in VAT mass, nor in inflammatory markers, insulin and leptin signaling (leptin receptor and SOCS3 expression) and appetite regulation (NPY, AgRP, POMC and CART) in the hypothalamus.
Conclusions 
The results suggest that fructose overconsumption causes alterations in pro-inflammatory markers and reduces insulin signaling in the VAT of female rats. These alterations could be one of the first consequences of fructose overconsumption, since they were detected in the absence of obesity, and hypothalamic inflammation and insulin and leptin resistance.",
publisher = "Belgrade: Institute for Biological Research “Siniša Stanković”",
journal = "Program & Book of Abstracts : IUBMB Advanced School Nutrition, Metabolism and Aging",
title = "Effects Of Fructose-enriched Diet On Inflammation And Insulin Signaling In The Hypothalamus And Visceral Adipose Tissue Of Female Rats",
pages = "34",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3986"
}
Đorđević, A., Kovačević, S., Matić, G.,& Elaković, I.. (2018). Effects Of Fructose-enriched Diet On Inflammation And Insulin Signaling In The Hypothalamus And Visceral Adipose Tissue Of Female Rats. in Program & Book of Abstracts : IUBMB Advanced School Nutrition, Metabolism and Aging
Belgrade: Institute for Biological Research “Siniša Stanković”., 34.
https://hdl.handle.net/21.15107/rcub_ibiss_3986
Đorđević A, Kovačević S, Matić G, Elaković I. Effects Of Fructose-enriched Diet On Inflammation And Insulin Signaling In The Hypothalamus And Visceral Adipose Tissue Of Female Rats. in Program & Book of Abstracts : IUBMB Advanced School Nutrition, Metabolism and Aging. 2018;:34.
https://hdl.handle.net/21.15107/rcub_ibiss_3986 .
Đorđević, Ana, Kovačević, Sanja, Matić, Gordana, Elaković, Ivana, "Effects Of Fructose-enriched Diet On Inflammation And Insulin Signaling In The Hypothalamus And Visceral Adipose Tissue Of Female Rats" in Program & Book of Abstracts : IUBMB Advanced School Nutrition, Metabolism and Aging (2018):34,
https://hdl.handle.net/21.15107/rcub_ibiss_3986 .