TY  - JOUR
AU  - Zec, Manja M.
AU  - Krga, Irena
AU  - Stojković, Ljiljana
AU  - Živković, Maja
AU  - Pokimica, Biljana
AU  - Stanković, Aleksandra
AU  - Glibetić, Marija
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1085
AB  - Dietary polyphenols promote cardiometabolic health and are linked with long-chain polyunsaturated fatty acids in plasma phospholipids (LC-PUFA). The FADS2 polymorphisms are associated with LC-PUFA metabolism and overweight/obesity. This 4-week study examined the link between polyphenol intake, FADS2 variants (rs174593, rs174616, rs174576) and obesity in 62 overweight adults (BMI  gt = 25), allocated to consume 100 mL daily of either: Aronia juice, a rich source of polyphenols, with 1177.11 mg polyphenols (expressed as gallic acid equivalents)/100 mL (AJ, n = 22), Aronia juice with 294.28 mg polyphenols/100 mL (MJ, n = 20), or nutritionally matched polyphenol-lacking placebo as a control (PLB, n = 20). We analyzed LC-PUFA (% of total pool) by gas chromatography and FADS2 variants by real-time PCR. Four-week changes in LC-PUFA, BMI, and body weight were included in statistical models, controlling for gender and PUFA intake. Only upon AJ and MJ, the presence of FADS2 variant alleles affected changes in linoleic, arachidonic, and eicosapentaenoic acid (EPA). Upon MJ treatment, changes in EPA were inversely linked with changes in BMI (beta= -0.73, p = 0.029) and weight gain (beta= -2.17, p = 0.024). Only in subjects drinking AJ, the link between changes in EPA and anthropometric indices was modified by the rs174576 variant allele. Our results indicate the interaction between FADS2, fatty acid metabolism, and polyphenol intake in overweight subjects.
PB  - MDPI, Basel
T2  - Nutrients
T1  - Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?
IS  - 2
SP  - 296
VL  - 13
DO  - 10.3390/nu13020296
ER  - 

@article{
author = "Zec, Manja M. and Krga, Irena and Stojković, Ljiljana and Živković, Maja and Pokimica, Biljana and Stanković, Aleksandra and Glibetić, Marija",
year = "2021",
abstract = "Dietary polyphenols promote cardiometabolic health and are linked with long-chain polyunsaturated fatty acids in plasma phospholipids (LC-PUFA). The FADS2 polymorphisms are associated with LC-PUFA metabolism and overweight/obesity. This 4-week study examined the link between polyphenol intake, FADS2 variants (rs174593, rs174616, rs174576) and obesity in 62 overweight adults (BMI  gt = 25), allocated to consume 100 mL daily of either: Aronia juice, a rich source of polyphenols, with 1177.11 mg polyphenols (expressed as gallic acid equivalents)/100 mL (AJ, n = 22), Aronia juice with 294.28 mg polyphenols/100 mL (MJ, n = 20), or nutritionally matched polyphenol-lacking placebo as a control (PLB, n = 20). We analyzed LC-PUFA (% of total pool) by gas chromatography and FADS2 variants by real-time PCR. Four-week changes in LC-PUFA, BMI, and body weight were included in statistical models, controlling for gender and PUFA intake. Only upon AJ and MJ, the presence of FADS2 variant alleles affected changes in linoleic, arachidonic, and eicosapentaenoic acid (EPA). Upon MJ treatment, changes in EPA were inversely linked with changes in BMI (beta= -0.73, p = 0.029) and weight gain (beta= -2.17, p = 0.024). Only in subjects drinking AJ, the link between changes in EPA and anthropometric indices was modified by the rs174576 variant allele. Our results indicate the interaction between FADS2, fatty acid metabolism, and polyphenol intake in overweight subjects.",
publisher = "MDPI, Basel",
journal = "Nutrients",
title = "Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?",
number = "2",
pages = "296",
volume = "13",
doi = "10.3390/nu13020296"
}

Zec, M. M., Krga, I., Stojković, L., Živković, M., Pokimica, B., Stanković, A.,& Glibetić, M.. (2021). Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?. in Nutrients
MDPI, Basel., 13(2), 296.
https://doi.org/10.3390/nu13020296

Zec MM, Krga I, Stojković L, Živković M, Pokimica B, Stanković A, Glibetić M. Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?. in Nutrients. 2021;13(2):296.
doi:10.3390/nu13020296 .

Zec, Manja M., Krga, Irena, Stojković, Ljiljana, Živković, Maja, Pokimica, Biljana, Stanković, Aleksandra, Glibetić, Marija, "Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?" in Nutrients, 13, no. 2 (2021):296,
https://doi.org/10.3390/nu13020296 . .

TY  - JOUR
AU  - Stojković, Ljiljana
AU  - Zec, Manja
AU  - Živković, Maja
AU  - Bundalo, Maja
AU  - Bošković, Maja
AU  - Glibetić, Marija
AU  - Stankovic, Aleksandra
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1148
AB  - Cardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to determine the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice (AMJ) treatment on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects (n = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, MTHFR C677T gene variant, anthropometric and metabolic parameters) modulated the LINE-1 methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of LINE-1 methylation was done by MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas–liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women (n = 22), we observed significant decreases in LINE-1 methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; P = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96–89.58), respectively; P = 0.02]. The change (after vs. before treatment) in LINE-1 methylation directly correlated with the presence of MTHFR 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols (R = 0.72, R2 = 0.52, adjusted R2 = 0.36, P = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD.
PB  - Frontiers Media S.A.
T2  - Frontiers in Nutrition
T1  - Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women
VL  - 8
DO  - 10.3389/fnut.2021.689055
ER  - 

@article{
author = "Stojković, Ljiljana and Zec, Manja and Živković, Maja and Bundalo, Maja and Bošković, Maja and Glibetić, Marija and Stankovic, Aleksandra",
year = "2021",
abstract = "Cardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to determine the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice (AMJ) treatment on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects (n = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, MTHFR C677T gene variant, anthropometric and metabolic parameters) modulated the LINE-1 methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of LINE-1 methylation was done by MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas–liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women (n = 22), we observed significant decreases in LINE-1 methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; P = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96–89.58), respectively; P = 0.02]. The change (after vs. before treatment) in LINE-1 methylation directly correlated with the presence of MTHFR 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols (R = 0.72, R2 = 0.52, adjusted R2 = 0.36, P = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Nutrition",
title = "Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women",
volume = "8",
doi = "10.3389/fnut.2021.689055"
}

Stojković, L., Zec, M., Živković, M., Bundalo, M., Bošković, M., Glibetić, M.,& Stankovic, A.. (2021). Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women. in Frontiers in Nutrition
Frontiers Media S.A.., 8.
https://doi.org/10.3389/fnut.2021.689055

Stojković L, Zec M, Živković M, Bundalo M, Bošković M, Glibetić M, Stankovic A. Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women. in Frontiers in Nutrition. 2021;8.
doi:10.3389/fnut.2021.689055 .

Stojković, Ljiljana, Zec, Manja, Živković, Maja, Bundalo, Maja, Bošković, Maja, Glibetić, Marija, Stankovic, Aleksandra, "Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women" in Frontiers in Nutrition, 8 (2021),
https://doi.org/10.3389/fnut.2021.689055 . .

TY  - JOUR
AU  - Zec, Manja M.
AU  - Stojković, Ljiljana
AU  - Zeković, Milica
AU  - Pokimica, Biljana
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Glibetić, Marija
PY  - 2020
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/996
AB  - Polymorphisms in FADS genes are associated with plasma long-chain polyunsaturated fatty acids (LC-PUFA) and modulate omega-6/omega-3 balance. We hypothesized that the FADS2 gene variants will be associated with lower product-to-precursor ratio in the fatty acid metabolic pathways. Thus, we explored FADS2 rs174593, rs174616, and rs174576 effects on plasma phospholipid fatty acid profile, markers of desaturase activities, and risk factors in a sample of apparently healthy Serbian adults. Food and nutrient intake data were compiled through 24 h recalls. Plasma phospholipid fatty acid content was assessed by gaschromatography. Estimated desaturase activities were calculated as conversion rates towards LC-PUFA in omega-6 pathway. During the selection of FADS2 polymorphisms, we accounted for their positional and functional aspect. Genotyping was performed by Real Time PCR. Multivariable-adjusted general linear and hierarchical regression models were applied. Study subjects (mean age = 40 +/- 7 years, 70% who were overweight) had a median dietary omega-6/omega-3 ratio of 16.29. Alternative allele frequencies were 33%, 36%, and 51% for rs174593, rs174576, and rs174616, respectively. Addition of FADS2 alternative alleles was associated with lower plasma arachidonic acid (AA, C20:4 n-6, P  lt  .001) and estimated desaturase-5 activity (P  lt  .001), irrespective of gender, age, daily polyunsaturated/saturated fatty acid intake, and obesity. The rs174576 association with AA withstood multiple testing and additional adjustments for other variants (multivariable-adjusted beta = -1.14 [95% CI: - 2.25, -0.43]). None of the variants was associated with dietary intake, serum lipids, or obesity. We observed inverse associations between FADS2 variants and plasma AA but not omega-3 fatty acids in Serbian subjects, with rs174576 exhibiting the strongest relation.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Nutrition Research
T1  - FADS2 polymorphisms are associated with plasma arachidonic acid and estimated desaturase-5 activity in a cross-sectional study
EP  - 62
SP  - 49
VL  - 83
DO  - 10.1016/j.nutres.2020.08.010
ER  - 

@article{
author = "Zec, Manja M. and Stojković, Ljiljana and Zeković, Milica and Pokimica, Biljana and Živković, Maja and Stanković, Aleksandra and Glibetić, Marija",
year = "2020",
abstract = "Polymorphisms in FADS genes are associated with plasma long-chain polyunsaturated fatty acids (LC-PUFA) and modulate omega-6/omega-3 balance. We hypothesized that the FADS2 gene variants will be associated with lower product-to-precursor ratio in the fatty acid metabolic pathways. Thus, we explored FADS2 rs174593, rs174616, and rs174576 effects on plasma phospholipid fatty acid profile, markers of desaturase activities, and risk factors in a sample of apparently healthy Serbian adults. Food and nutrient intake data were compiled through 24 h recalls. Plasma phospholipid fatty acid content was assessed by gaschromatography. Estimated desaturase activities were calculated as conversion rates towards LC-PUFA in omega-6 pathway. During the selection of FADS2 polymorphisms, we accounted for their positional and functional aspect. Genotyping was performed by Real Time PCR. Multivariable-adjusted general linear and hierarchical regression models were applied. Study subjects (mean age = 40 +/- 7 years, 70% who were overweight) had a median dietary omega-6/omega-3 ratio of 16.29. Alternative allele frequencies were 33%, 36%, and 51% for rs174593, rs174576, and rs174616, respectively. Addition of FADS2 alternative alleles was associated with lower plasma arachidonic acid (AA, C20:4 n-6, P  lt  .001) and estimated desaturase-5 activity (P  lt  .001), irrespective of gender, age, daily polyunsaturated/saturated fatty acid intake, and obesity. The rs174576 association with AA withstood multiple testing and additional adjustments for other variants (multivariable-adjusted beta = -1.14 [95% CI: - 2.25, -0.43]). None of the variants was associated with dietary intake, serum lipids, or obesity. We observed inverse associations between FADS2 variants and plasma AA but not omega-3 fatty acids in Serbian subjects, with rs174576 exhibiting the strongest relation.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Nutrition Research",
title = "FADS2 polymorphisms are associated with plasma arachidonic acid and estimated desaturase-5 activity in a cross-sectional study",
pages = "62-49",
volume = "83",
doi = "10.1016/j.nutres.2020.08.010"
}

Zec, M. M., Stojković, L., Zeković, M., Pokimica, B., Živković, M., Stanković, A.,& Glibetić, M.. (2020). FADS2 polymorphisms are associated with plasma arachidonic acid and estimated desaturase-5 activity in a cross-sectional study. in Nutrition Research
Pergamon-Elsevier Science Ltd, Oxford., 83, 49-62.
https://doi.org/10.1016/j.nutres.2020.08.010

Zec MM, Stojković L, Zeković M, Pokimica B, Živković M, Stanković A, Glibetić M. FADS2 polymorphisms are associated with plasma arachidonic acid and estimated desaturase-5 activity in a cross-sectional study. in Nutrition Research. 2020;83:49-62.
doi:10.1016/j.nutres.2020.08.010 .

Zec, Manja M., Stojković, Ljiljana, Zeković, Milica, Pokimica, Biljana, Živković, Maja, Stanković, Aleksandra, Glibetić, Marija, "FADS2 polymorphisms are associated with plasma arachidonic acid and estimated desaturase-5 activity in a cross-sectional study" in Nutrition Research, 83 (2020):49-62,
https://doi.org/10.1016/j.nutres.2020.08.010 . .

TY  - JOUR
AU  - Stojković, Ljiljana
AU  - Jovanović, Ivan
AU  - Živković, Maja
AU  - Zec, Manja M.
AU  - Đurić, Tamara
AU  - Životić, Ivan
AU  - Kuveljić, Jovana
AU  - Kolaković, Ana
AU  - Kolić, Ivana
AU  - Đorđević, Ana
AU  - Glibetić, Marija
AU  - Alavantić, Dragan
AU  - Stanković, Aleksandra
PY  - 2020
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1060
AB  - Foods and food products that contain polyphenols are proposed to modulate risk of cardiovascular disease. The aim of this three-arm, crossover, randomized, double-blind, placebo-controlled intervention study was to examine the impact ofAronia melanocarpajuice (AMJ), high-polyphenol (AMJ treatment, 1.17 g/100 mL polyphenols) and low-polyphenol (dAMJ treatment, 0.29 g/100 mL polyphenols) dose, on the transcriptome in peripheral blood mononuclear cells (PBMC) of 19 subjects at cardiovascular risk. Transcriptome data were obtained by microarray. Bioinformatic functional annotation analysis was performed on both the whole transcriptome datasets and the differentially expressed genes (DEGs). Expression of selected DEGs was validated by RT-qPCR. Administration of AMJ and dAMJ treatments during the two consecutive four-week treatment periods had additive effects on PBMC transcriptome profiles, with the most pronounced and specific effect noticed for AMJ in the last treatment period (TP3) of the trial. Between the high-dose and low-dose treatments in TP3, there was a multitude of overlapping DEGs and DEG-enriched biological processes and pathways, which primarily included immunomodulation and regulation of cell proliferation/death. Increased expression ofTNF,IL1B,IL8,RGS1,OSM, andDUSP2in TP3 was confirmed by RT-qPCR. The results suggest the immunomodulatory effects of prolonged habitual consumption of polyphenol-rich aronia juice in individuals at cardiovascular risk.
PB  - MDPI, Basel
T2  - Nutrients
T1  - The Effects ofAronia melanocarpaJuice Consumption on the mRNA Expression Profile in Peripheral Blood Mononuclear Cells in Subjects at Cardiovascular Risk
IS  - 5
VL  - 12
DO  - 10.3390/nu12051484
ER  - 

@article{
author = "Stojković, Ljiljana and Jovanović, Ivan and Živković, Maja and Zec, Manja M. and Đurić, Tamara and Životić, Ivan and Kuveljić, Jovana and Kolaković, Ana and Kolić, Ivana and Đorđević, Ana and Glibetić, Marija and Alavantić, Dragan and Stanković, Aleksandra",
year = "2020",
abstract = "Foods and food products that contain polyphenols are proposed to modulate risk of cardiovascular disease. The aim of this three-arm, crossover, randomized, double-blind, placebo-controlled intervention study was to examine the impact ofAronia melanocarpajuice (AMJ), high-polyphenol (AMJ treatment, 1.17 g/100 mL polyphenols) and low-polyphenol (dAMJ treatment, 0.29 g/100 mL polyphenols) dose, on the transcriptome in peripheral blood mononuclear cells (PBMC) of 19 subjects at cardiovascular risk. Transcriptome data were obtained by microarray. Bioinformatic functional annotation analysis was performed on both the whole transcriptome datasets and the differentially expressed genes (DEGs). Expression of selected DEGs was validated by RT-qPCR. Administration of AMJ and dAMJ treatments during the two consecutive four-week treatment periods had additive effects on PBMC transcriptome profiles, with the most pronounced and specific effect noticed for AMJ in the last treatment period (TP3) of the trial. Between the high-dose and low-dose treatments in TP3, there was a multitude of overlapping DEGs and DEG-enriched biological processes and pathways, which primarily included immunomodulation and regulation of cell proliferation/death. Increased expression ofTNF,IL1B,IL8,RGS1,OSM, andDUSP2in TP3 was confirmed by RT-qPCR. The results suggest the immunomodulatory effects of prolonged habitual consumption of polyphenol-rich aronia juice in individuals at cardiovascular risk.",
publisher = "MDPI, Basel",
journal = "Nutrients",
title = "The Effects ofAronia melanocarpaJuice Consumption on the mRNA Expression Profile in Peripheral Blood Mononuclear Cells in Subjects at Cardiovascular Risk",
number = "5",
volume = "12",
doi = "10.3390/nu12051484"
}

Stojković, L., Jovanović, I., Živković, M., Zec, M. M., Đurić, T., Životić, I., Kuveljić, J., Kolaković, A., Kolić, I., Đorđević, A., Glibetić, M., Alavantić, D.,& Stanković, A.. (2020). The Effects ofAronia melanocarpaJuice Consumption on the mRNA Expression Profile in Peripheral Blood Mononuclear Cells in Subjects at Cardiovascular Risk. in Nutrients
MDPI, Basel., 12(5).
https://doi.org/10.3390/nu12051484

Stojković L, Jovanović I, Živković M, Zec MM, Đurić T, Životić I, Kuveljić J, Kolaković A, Kolić I, Đorđević A, Glibetić M, Alavantić D, Stanković A. The Effects ofAronia melanocarpaJuice Consumption on the mRNA Expression Profile in Peripheral Blood Mononuclear Cells in Subjects at Cardiovascular Risk. in Nutrients. 2020;12(5).
doi:10.3390/nu12051484 .

Stojković, Ljiljana, Jovanović, Ivan, Živković, Maja, Zec, Manja M., Đurić, Tamara, Životić, Ivan, Kuveljić, Jovana, Kolaković, Ana, Kolić, Ivana, Đorđević, Ana, Glibetić, Marija, Alavantić, Dragan, Stanković, Aleksandra, "The Effects ofAronia melanocarpaJuice Consumption on the mRNA Expression Profile in Peripheral Blood Mononuclear Cells in Subjects at Cardiovascular Risk" in Nutrients, 12, no. 5 (2020),
https://doi.org/10.3390/nu12051484 . .