Glucocorticoid Signaling Alterations Induced by Late-Onset Dietary Resctriction Aggravate Metabolic Inflammation in the Liver of Old Wistar Rats
2021
Аутори:
Teofilović, AnaVratarić, Miloš
Veličković, Nataša
Vojnović-Milutinović, Danijela
Prvulović, Milica
Todorović, Smilja
Mladenović, Aleksandra
Đorđević, Ana
Остала ауторства
Gabbianelli, RositaТип документа:
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Objectives: Dietary restriction (DR) is the approach often used
to delay the development of age-related disorders. One of the unresolved
questions is how late beginning and short duration of DR
affects disturbed metabolic balance caused by ageing. Glucocorticoid
hormones have significant role in the regulation of energy metabolism
and inflammation, especially during ageing when their
systemic
concentration arise. The aim of this study was to examine
the impact of glucocorticoid signaling alterations induced by the
late-onset DR on metabolic inflammation in the liver of old Wistar
rats.
Methods: The experiments were conducted on 6- and
24‑month‑old male Wistar rats on ad libitum diet and
24‑month‑old animals on restrictive diet (60% of ad libitum daily
intake) from 21st to 24th month (late-onset DR). The gene expression
of proinflammatory cytokines was measured by qPCR, while
protein levels of nuclear factor κB (NFκB) and antioxidant enzymes
were determined by Western blot. Glucocorticoid signaling was
analyzed at the level of glucocorticoid prereceptor metabolism and
subcellular distribution of glucocorticoid receptor (GR). Liver corticosterone
concentration was measured by ELISA.
Results: Decreased levels of antioxidant enzymes observed
during ageing were accompanied with augmented inflammation,
characterized by increased nuclear NFκB protein level and higher
expression of Toll like receptor 4 and TNFα. Corticosterone concentration
in the liver of old rats was increased despite unchanged
level of proteins involved in glucocorticoid prereceptor metabolism.
Late-onset DR reduced adipose tissue and liver mass of old
animals, and further stimulated inflammation in the liver.
Decreased level of hepatic corticosterone after DR was a consequence
of increased expression of 5α-reductase which was in
agreement with the decreased GR protein level in the nuclear
fraction.
Conclusion: Late-onset DR did not improve expression of antioxidant
enzymes and led to progression of age-related inflammation
in the liver. This was accompanied with decreased levels of
corticosterone and GR in the nucleus implying that late-onset DR
aggravates inflammatory response through decreased glucocorticoid
signaling in the liver of old rats.
Кључне речи:
dietary restriction; ageing; energy metabolism; inflammation; glucocorticoidsФинансирање / 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)
У:
- Proceedings from the 4th European Summer School on Nutrigenomics (ESSN 2021); 2021 Jun 21-25; Online. Basel: S Karger AG; 2021. p. 13. (Lifestyle Genomics)