Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age
2023
Аутори:
Šošić-Jurjević, BrankaLütjohann, Dieter
Trifunović, Svetlana
Pavlović, Slađan
Borković-Mitić, Slavica
Jovanović, Ljubiša
Ristić, Nataša
Ljiljana, Marina
Ajdžanović, Vladimir
Filipović, Branko
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
Sex differences; Age; Cholesterol metabolism; Oxidative stress; Liver; Small intestineИзвор:
International Journal of Molecular Sciences, 2023, 24, 16, 12624-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
DOI: 10.3390/ijms241612624
ISSN: 1661-6596
PubMed: 37628805