Hepatic inflammation induced by high-fructose diet is associated with altered 11 beta HSD1 expression in the liver of Wistar rats
2014
Аутори:
Teofilović, AnaBursac, Biljana
Đorđević, Ana
Vojnović-Milutinović, Danijela
Radovanović, Marina
Matić, Gordana
Velickovic, Natasa
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
High fructose consumption provokes metabolic perturbations that result
in chronic low-grade inflammation and insulin resistance.
Glucocorticoids, potent anti-inflammatory hormones, have important role
in pathogenesis of diet-induced metabolic disturbances. The aim of this
study was to examine the link between glucocorticoid metabolism and
inflammation in the liver of fructose-fed rats.
Fructose-fed male Wistar rats consumed 60 \% fructose solution for 9
weeks. Glucocorticoid prereceptor metabolism and signaling were analyzed
by measuring the level of 11 beta-hydroxysteroid dehydrogenase type 1
(11 beta HSD1) and hexose-6-phosphate dehydrogenase expression, as well
as via determination of intracellular corticosterone concentration,
glucocorticoid receptor subcellular distribution and expression of its
target gene, phosphoenolpyruvate carboxykinase. Nuclear factor kappa B
(NF kappa B), tumor necrosis factor alpha (TNF alpha) and the level of
inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1) on
Ser(307) were analyzed as markers of hepatic inflammation. The protein
and/or mRNA levels of all examined molecules were assessed by Western
blot and/or qPCR.
Fructose-rich diet led to an enhancement of 11 beta HSD1 protein level
in the liver, without affecting intracellular level of corticosterone
and downstream glucocorticoid signaling. On the other hand,
proinflammatory state was achieved through NF kappa B activation and
increased TNF alpha expression, while elevated level of inhibitory
phosphorylation of IRS-1 was observed as an early hallmark of insulin
resistance.
High-fructose diet does not influence hepatic glucocorticoid signaling
downstream of the receptor, permitting development of NF kappa B-driven
inflammation. The alteration in 11 beta HSD1 expression is most likely
the consequence of enhanced inflammation, finally leading to disruption
of insulin signaling in the rat liver.
Кључне речи:
11 beta HSD1; Glucocorticoids; Inflammation; Fructose; LiverИзвор:
European Journal of Nutrition, 2014, 53, 6, 1393-1402
DOI: 10.1007/s00394-013-0641-4
ISSN: 1436-6215