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 . .