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

Abstract

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, 11β-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.

Temporal effect of fructose supplementation at different concentrations on hepatic metabolism of Wistar rats

“…Studies have demonstrated that the administration of 10 % fructose in water for 3 weeks to healthy Wistar rats is associated with a state of oxidative stress due to an imbalance between production of ROS and antioxidant capacity (33,34). In addition, it is known that the incidence and progression of various health conditions, such as liver steatosis and other conditions, correlate with variations in oxidative stress and antioxidant defense enzyme levels (35).…”

Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats

“…For the measurement of xanthine oxidase activity, the adipose tissue was homogenized in 100 mMTris buffer (pH 7.4) containing protease inhibitors and sonicated (3 × 15 s at 10 MHz on ice) prior to 20 min centrifugation at 20,000 × g (4 °C). Hepatic cell extracts were prepared as described previously ( 56 ). Xanthine oxidase activity was measured spectrophotometrically on the Synergy H1 Hybrid Multi-Mode Reader (BioTek Instruments, Winooski, VT, United States) by estimating the rate of oxidation of xanthine to uric acid at 295 nm ( 57 ).…”

Overview and prospect of NAFLD: Significant roles of nutrients and dietary patterns in its progression or prevention

“…After consuming 60% fructose solution for 9 weeks, both male and female Wistar rats showed increased hepatic TNF alpha (TNFα), one of the markers of inflammation. 47 , 48 However, NFκB activation was only detected in male rats, which may be due to the protection effect of the enhanced glucocorticoid signaling restricted to female rats. 48 Intriguingly, consuming fructose under stressful conditions, as performed by Kovačević et al 49 in female Wistar rats, counteracted the effects of stress on hepatic lipid accumulation alone.…”

“… 47 , 48 However, NFκB activation was only detected in male rats, which may be due to the protection effect of the enhanced glucocorticoid signaling restricted to female rats. 48 Intriguingly, consuming fructose under stressful conditions, as performed by Kovačević et al 49 in female Wistar rats, counteracted the effects of stress on hepatic lipid accumulation alone. Whether this is also a secondary effect of the elevated glucocorticoids remains unknown.…”