Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats.

The effects of early-life fructose consumption on hepatic signaling pathways and their relation to the development of metabolic disorders in later life are not fully understood. To investigate whether fructose overconsumption at a young age induces alterations in glucocorticoid signaling that might contribute to development of metabolic disturbances, we analysed glucocorticoid receptor hormone-binding parameters and expression of its target genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) and lipid metabolism (lipin-1), as well as redox and inflammatory status in the liver of female rats subjected to a fructose-rich diet immediately after weaning. The fructose diet increased hepatic corticosterone concentration, 11ß-hydroxysteroid dehydrogenase type 1 level, glucocorticoid receptor protein level and hormone-binding activity, as well as lipin-1 level. The expression of glucose-6-phosphatase was reduced in fructose-fed rats, while phosphoenolpyruvate carboxykinase remained unaltered. The fructose-rich diet increased the level of fructose transporter GLUT2, while the expression of fructolytic enzymes fructokinase and aldolase B remained unaltered. The diet also affected pro-inflammatory pathways, but had no effect on the antioxidant defence system. In conclusion, a fructose-rich diet applied immediately after weaning promoted lipogenesis and enhanced hepatic glucocorticoid signaling, possibly to protect against inflammatory damage, but without an effect on gluconeogenesis and antioxidant enzymes. Yet, prolonged treatment might ultimately lead to more pronounced metabolic disturbances.

The expression and activity of antioxidant enzymes in the liver of rats exposed to high-fructose diet in the period from weaning to adulthood.

BACKGROUND: Increased fructose consumption correlates with rising prevalence of various metabolic disorders, some of which were linked to oxidative stress. The relationship between fructose consumption and oxidative stress is complex and effects of a fructose-rich diet on the young population have not been fully elucidated. The aim of this study was to investigate whether high-fructose diet applied in the period from weaning to adulthood induces oxidative stress in the liver, thus contributing to induction or aggravation of metabolic disturbances in later adulthood. To that end we examined the effects of high-fructose diet on expression and activity of antioxidant enzymes, markers of lipid peroxidation and protein damage in the liver as the main fructose metabolizing tissue. RESULTS: High-fructose diet increased only SOD2 (mitochondrial manganese superoxide dismutase) activity, with no effect on other antioxidant enzymes, lipid peroxidation or accumulation of damaged proteins in the liver. CONCLUSION: The results show that fructose-induced metabolic disturbances could not be attributed to oxidative stress, at least not at young age. The absence of oxidative stress in the liver observed herein implies that young organisms are capable of maintaining redox homeostasis when challenged by fructose-derived energy overload.

Long-term fructose-enriched diet introduced immediately after weaning does not induce oxidative stress in the rat liver.

Increased fructose consumption is correlated with the rising prevalence of obesity, metabolic syndrome, and type 2 diabetes. It is believed that reactive oxygen species contribute to the development and progression of metabolic disturbances, especially those associated with insulin resistance. Dietary fructose produces both pro-oxidative and antioxidative effects, depending upon the experimental conditions, dosage, duration of treatment, and pathophysiological milieu. The effects of fructose overconsumption on young populations, which have an increased risk of developing metabolic disorders in adulthood, have not been fully elucidated. We have previously shown that rats subjected to a long-term fructose-enriched diet immediately after weaning display impaired hepatic insulin sensitivity. In this study, we tested the hypothesis that long-term fructose consumption induces alterations in the redox setting of the liver. Starting from the 21st day after birth, male Wistar rats were maintained for 9 weeks on a standard diet (control) or a fructose-enriched diet that consisted of standard food and 10% fructose solution instead of drinking water. The expression and activity of antioxidant enzymes as well as lipid peroxidation and protein damage markers were measured. The results showed that a fructose-enriched diet led to an increased expression of mitochondrial manganese superoxide dismutase but did not affect antioxidant enzymes activity, lipid peroxidation, thiol content, and the level of protein oxidation. Therefore, our results suggest that the decrease in hepatic insulin sensitivity that was previously observed in rats that were kept on the same diet regime might be attributed to molecular mechanisms other than redox disbalance. A possible fructose-related micronutrient deficiency should be examined.