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01.09.2014 | Original Contribution

Hepatic inflammation induced by high-fructose diet is associated with altered 11βHSD1 expression in the liver of Wistar rats

verfasst von: Ana Vasiljević, Biljana Bursać, Ana Djordjevic, Danijela Vojnović Milutinović, Marina Nikolić, Gordana Matić, Nataša Veličković

Erschienen in: European Journal of Nutrition | Ausgabe 6/2014

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Abstract

Purpose

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.

Methods

Fructose-fed male Wistar rats consumed 60 % fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and signaling were analyzed by measuring the level of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) 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 (NFκB), tumor necrosis factor alpha (TNFα) and the level of inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1) on Ser³⁰⁷ 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.

Results

Fructose-rich diet led to an enhancement of 11βHSD1 protein level in the liver, without affecting intracellular level of corticosterone and downstream glucocorticoid signaling. On the other hand, proinflammatory state was achieved through NFκB activation and increased TNFα expression, while elevated level of inhibitory phosphorylation of IRS-1 was observed as an early hallmark of insulin resistance.

Conclusion

High-fructose diet does not influence hepatic glucocorticoid signaling downstream of the receptor, permitting development of NFκB-driven inflammation. The alteration in 11βHSD1 expression is most likely the consequence of enhanced inflammation, finally leading to disruption of insulin signaling in the rat liver.

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Titel: Hepatic inflammation induced by high-fructose diet is associated with altered 11βHSD1 expression in the liver of Wistar rats
verfasst von: Ana Vasiljević
Biljana Bursać
Ana Djordjevic
Danijela Vojnović Milutinović
Marina Nikolić
Gordana Matić
Nataša Veličković
Publikationsdatum: 01.09.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nutrition / Ausgabe 6/2014
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-013-0641-4

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