@article{
author = "Kovačević, Sanja and Elaković, Ivana and Vojnović-Milutinović, Danijela and Nikolić-Kokić, Aleksandra and Blagojević, Duško and Matić, Gordana and Tappy, Luc and Đorđević, Ana and Brkljačić, Jelena",
year = "2021",
abstract = "Background: Both fructose consumption and chronic stress contribute to the development of metabolic disorders.
The consequences of such combination are not fully understood.
Objective: We investigated whether fructose supplementation and chronic stress synergistically disturb hepatic lipid
and glucose metabolism. The role of energy sensing, redox, and inflammatory status during development of metabolic
disturbances was investigated.
Methods: Female Wistar rats, aged 2.5 mo, were divided into 4 experimental groups: control (C) fed a standard diet
(commercial food and drinking water); fructose (F) fed the same food and 10% fructose solution; stress (S) fed the
standard diet and subjected to chronic unpredictable stress and, stress + fructose (SF) combining conditions F and
S as above. Stress included daily stressors: cold water forced swimming, physical restraint, cold room, wet bedding,
rocking, switching, or tilting cages. After 9 wk, hepatic enzymes and transcription factors involved in gluconeogenesis,
lipogenesis, fatty acid oxidation, antioxidative defence, energy sensing, and cytokines were assessed by qPCR, Western
blotting, and spectrophotometry and analyzed by 2-factor ANOVA.
Results: Fructose increased AMP-activated protein kinase (AMPK) phosphorylation (40%; P < 0.05) and the ratio of
inhibitory phosphorylation to total acetyl-CoA carboxylase (46%; P < 0.01), and decreased sterol regulatory element
binding protein 1c nuclear translocation by 30% (P < 0.05) in F and SF compared with C rats. Increased phosPck
(phoenolpyruvate carboxykinase) (85%) and G6pase (glucose-6-phosphatase) (55%) was observed in S rats (P < 0.05).
A 40% decrease in Apob (apolipoprotein B-100) and an increase in hepatic lipids (P < 0.05), together with a double
increase in TNF-α (P < 0.001), were observed in S rats, but without liver histopathological changes. These stress effects
on lipid accumulation and TNF-α were abolished in SF rats (P < 0.05).
Conclusions: Fructose does not enhance stress effects on hepatic lipid and glucose metabolism but attenuates its
effects on hepatic lipid accumulation and inflammation, suggesting that, in female rats, AMPK activation prevails over
stress-induced effects.",
publisher = "Oxford University Press on behalf of the American Society of Nutrition",
journal = "The Journal of Nutrition",
title = "Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats",
number = "12",
volume = "151",
doi = "10.1093/jn/nxab294",
pages = "3661-3670"
}