TY  - JOUR
AU  - Šošić-Jurjević, Branka
AU  - Lütjohann, Dieter
AU  - Trifunović, Svetlana
AU  - Pavlović, Slađan
AU  - Borković-Mitić, Slavica
AU  - Jovanović, Ljubiša
AU  - Ristić, Nataša
AU  - Ljiljana, Marina
AU  - Ajdžanović, Vladimir
AU  - Filipović, Branko
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6120
AB  - Age and sex influence serum cholesterol levels, but the underlying mechanisms remain
unclear. To investigate further, we measured cholesterol, precursors (surrogate synthesis markers),
degradation products (oxysterols and bile acid precursors) in serum, the liver, jejunum, and ileum,
as well as serum plant sterols (intestinal absorption markers) in male and female Wistar rats (4 and
24 months old). The analysis of histomorphometric and oxidative stress parameters (superoxide
dismutase, catalase, glutathione-related enzyme activities, lipid peroxide, and protein carbonyl concentrations) in the liver and jejunum offered further insights into the age- and sex-related differences.
The hepatic gene expression analysis included AR, ERα, and sex-specific growth hormone-regulated
(Cyp2c11 and Cyp2c12) and thyroid-responsive (Dio1, Tbg, and Spot 14) genes by qPCR. We observed
age-related changes in both sexes, with greater prominence in females. Aged females had significantly
higher serum cholesterol (p < 0.05), jejunum cholesterol (p < 0.05), and serum plant sterols (p < 0.05).
They exhibited poorer hepato-intestinal health compared with males, which was characterized by
mild liver dysfunction (hydropic degeneration, increased serum ALT, p < 0.05, and decreased activity
of some antioxidant defense enzymes, p < 0.05), mononuclear inflammation in the jejunal lamina
propria, and age-related decreases in jejunal catalase and glutathione peroxidase activity (p < 0.05).
Aged females showed increased levels of 27-hydroxycholesterol (p < 0.05) and upregulated ERα gene
expression (p < 0.05) in the liver. Our study suggests that the more significant age-related increase in
serum cholesterol in females is associated with poorer hepato-intestinal health and increased jejunal
cholesterol absorption. The local increase in 27-hydroxycholesterol during aging might reduce the
hepatoprotective effects of endogenous estrogen in the female liver.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age
IS  - 16
VL  - 24
DO  - 10.3390/ijms241612624
SP  - 12624
ER  - 

@article{
author = "Šošić-Jurjević, Branka and Lütjohann, Dieter and Trifunović, Svetlana and Pavlović, Slađan and Borković-Mitić, Slavica and Jovanović, Ljubiša and Ristić, Nataša and Ljiljana, Marina and Ajdžanović, Vladimir and Filipović, Branko",
year = "2023",
abstract = "Age and sex influence serum cholesterol levels, but the underlying mechanisms remain
unclear. To investigate further, we measured cholesterol, precursors (surrogate synthesis markers),
degradation products (oxysterols and bile acid precursors) in serum, the liver, jejunum, and ileum,
as well as serum plant sterols (intestinal absorption markers) in male and female Wistar rats (4 and
24 months old). The analysis of histomorphometric and oxidative stress parameters (superoxide
dismutase, catalase, glutathione-related enzyme activities, lipid peroxide, and protein carbonyl concentrations) in the liver and jejunum offered further insights into the age- and sex-related differences.
The hepatic gene expression analysis included AR, ERα, and sex-specific growth hormone-regulated
(Cyp2c11 and Cyp2c12) and thyroid-responsive (Dio1, Tbg, and Spot 14) genes by qPCR. We observed
age-related changes in both sexes, with greater prominence in females. Aged females had significantly
higher serum cholesterol (p < 0.05), jejunum cholesterol (p < 0.05), and serum plant sterols (p < 0.05).
They exhibited poorer hepato-intestinal health compared with males, which was characterized by
mild liver dysfunction (hydropic degeneration, increased serum ALT, p < 0.05, and decreased activity
of some antioxidant defense enzymes, p < 0.05), mononuclear inflammation in the jejunal lamina
propria, and age-related decreases in jejunal catalase and glutathione peroxidase activity (p < 0.05).
Aged females showed increased levels of 27-hydroxycholesterol (p < 0.05) and upregulated ERα gene
expression (p < 0.05) in the liver. Our study suggests that the more significant age-related increase in
serum cholesterol in females is associated with poorer hepato-intestinal health and increased jejunal
cholesterol absorption. The local increase in 27-hydroxycholesterol during aging might reduce the
hepatoprotective effects of endogenous estrogen in the female liver.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age",
number = "16",
volume = "24",
doi = "10.3390/ijms241612624",
pages = "12624"
}

Šošić-Jurjević, B., Lütjohann, D., Trifunović, S., Pavlović, S., Borković-Mitić, S., Jovanović, L., Ristić, N., Ljiljana, M., Ajdžanović, V.,& Filipović, B.. (2023). Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age. in International Journal of Molecular Sciences
Basel: MDPI., 24(16), 12624.
https://doi.org/10.3390/ijms241612624

Šošić-Jurjević B, Lütjohann D, Trifunović S, Pavlović S, Borković-Mitić S, Jovanović L, Ristić N, Ljiljana M, Ajdžanović V, Filipović B. Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age. in International Journal of Molecular Sciences. 2023;24(16):12624.
doi:10.3390/ijms241612624 .

Šošić-Jurjević, Branka, Lütjohann, Dieter, Trifunović, Svetlana, Pavlović, Slađan, Borković-Mitić, Slavica, Jovanović, Ljubiša, Ristić, Nataša, Ljiljana, Marina, Ajdžanović, Vladimir, Filipović, Branko, "Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age" in International Journal of Molecular Sciences, 24, no. 16 (2023):12624,
https://doi.org/10.3390/ijms241612624 . .

TY  - JOUR
AU  - Šošić-Jurjević, Branka 
AU  - Lütjohann, Dieter
AU  - Renko, Kostja
AU  - Filipović, Branko
AU  - Radulović, Niko
AU  - Ajdžanović, Vladimir
AU  - Trifunović, Svetlana
AU  - Nestorović, Nataša
AU  - Živanović, Jasmina
AU  - Manojlović-Stojanoski, Milica
AU  - Kӧhrle, Josef
AU  - Milošević, Verica
PY  - 2019
UR  - internal-pdf://Šošić-Jurjević et al. - 2019 - The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Chol.pdf
UR  - https://www.sciencedirect.com/science/article/pii/S0960076018307507
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3290
AB  - We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.
T2  - The Journal of Steroid Biochemistry and Molecular Biology
T1  - The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats.
VL  - 190
DO  - 10.1016/j.jsbmb.2019.03.009
SP  - 1
EP  - 10
ER  - 

@article{
author = "Šošić-Jurjević, Branka  and Lütjohann, Dieter and Renko, Kostja and Filipović, Branko and Radulović, Niko and Ajdžanović, Vladimir and Trifunović, Svetlana and Nestorović, Nataša and Živanović, Jasmina and Manojlović-Stojanoski, Milica and Kӧhrle, Josef and Milošević, Verica",
year = "2019",
abstract = "We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.",
journal = "The Journal of Steroid Biochemistry and Molecular Biology",
title = "The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats.",
volume = "190",
doi = "10.1016/j.jsbmb.2019.03.009",
pages = "1-10"
}

Šošić-Jurjević, B., Lütjohann, D., Renko, K., Filipović, B., Radulović, N., Ajdžanović, V., Trifunović, S., Nestorović, N., Živanović, J., Manojlović-Stojanoski, M., Kӧhrle, J.,& Milošević, V.. (2019). The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats.. in The Journal of Steroid Biochemistry and Molecular Biology, 190, 1-10.
https://doi.org/10.1016/j.jsbmb.2019.03.009

Šošić-Jurjević B, Lütjohann D, Renko K, Filipović B, Radulović N, Ajdžanović V, Trifunović S, Nestorović N, Živanović J, Manojlović-Stojanoski M, Kӧhrle J, Milošević V. The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats.. in The Journal of Steroid Biochemistry and Molecular Biology. 2019;190:1-10.
doi:10.1016/j.jsbmb.2019.03.009 .

Šošić-Jurjević, Branka , Lütjohann, Dieter, Renko, Kostja, Filipović, Branko, Radulović, Niko, Ajdžanović, Vladimir, Trifunović, Svetlana, Nestorović, Nataša, Živanović, Jasmina, Manojlović-Stojanoski, Milica, Kӧhrle, Josef, Milošević, Verica, "The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats." in The Journal of Steroid Biochemistry and Molecular Biology, 190 (2019):1-10,
https://doi.org/10.1016/j.jsbmb.2019.03.009 . .

TY  - JOUR
AU  - Šošić-Jurjević, Branka 
AU  - Lütjohann, Dieter
AU  - Renko, Kostja
AU  - Filipović, Branko
AU  - Radulović, Niko
AU  - Ajdžanović, Vladimir
AU  - Trifunović, Svetlana
AU  - Nestorović, Nataša
AU  - Živanović, Jasmina
AU  - Manojlović-Stojanoski, Milica
AU  - Kӧhrle, Josef
AU  - Milošević, Verica
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0960076018307507
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3305
AB  - We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.
T2  - The Journal of Steroid Biochemistry and Molecular Miology
T1  - The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.
VL  - 190
DO  - 10.1016/j.jsbmb.2019.03.009
SP  - 1
EP  - 10
ER  - 

@article{
author = "Šošić-Jurjević, Branka  and Lütjohann, Dieter and Renko, Kostja and Filipović, Branko and Radulović, Niko and Ajdžanović, Vladimir and Trifunović, Svetlana and Nestorović, Nataša and Živanović, Jasmina and Manojlović-Stojanoski, Milica and Kӧhrle, Josef and Milošević, Verica",
year = "2019",
abstract = "We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.",
journal = "The Journal of Steroid Biochemistry and Molecular Miology",
title = "The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.",
volume = "190",
doi = "10.1016/j.jsbmb.2019.03.009",
pages = "1-10"
}

Šošić-Jurjević, B., Lütjohann, D., Renko, K., Filipović, B., Radulović, N., Ajdžanović, V., Trifunović, S., Nestorović, N., Živanović, J., Manojlović-Stojanoski, M., Kӧhrle, J.,& Milošević, V.. (2019). The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.. in The Journal of Steroid Biochemistry and Molecular Miology, 190, 1-10.
https://doi.org/10.1016/j.jsbmb.2019.03.009

Šošić-Jurjević B, Lütjohann D, Renko K, Filipović B, Radulović N, Ajdžanović V, Trifunović S, Nestorović N, Živanović J, Manojlović-Stojanoski M, Kӧhrle J, Milošević V. The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.. in The Journal of Steroid Biochemistry and Molecular Miology. 2019;190:1-10.
doi:10.1016/j.jsbmb.2019.03.009 .

Šošić-Jurjević, Branka , Lütjohann, Dieter, Renko, Kostja, Filipović, Branko, Radulović, Niko, Ajdžanović, Vladimir, Trifunović, Svetlana, Nestorović, Nataša, Živanović, Jasmina, Manojlović-Stojanoski, Milica, Kӧhrle, Josef, Milošević, Verica, "The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats." in The Journal of Steroid Biochemistry and Molecular Miology, 190 (2019):1-10,
https://doi.org/10.1016/j.jsbmb.2019.03.009 . .