Fructose enriched diet & stress

Apart from the sugary and highly caloric foods, contemporary lives of most people are characterized by daily exposure to different variants and intensities of chronic, unpredicted stressors. Glucocorticoids are probably best known precisely as one of the main stress-related hormones. Thus, since 2014, we focused our research on the glucocorticoid-linked metabolic effects of the 20% fructose dietary consumption and/or varied chronic low-grade stress treatments. Our results showed that chronic stress leads to VAT adipocyte size increase, as well as to the stimulation of the glucocorticoid/GR- regulated lipolysis decrease dependent on ATGL and HSL. On the other hand, fructose consumption leads to the increase of blood triglycerides, with the combined treatment causing an increased expression of lipogenic enzymes without the increase of adipocyte size, but with the concurrent release of newly synthetized free fatty acids directly into the circulation, i.e. dyslipidemia. Thus, we concluded that the combined treatment has more detrimental effects on the general metabolic status than the corresponding individual treatments^[1],[2],[3]. The analyses of the hepatic-related changes showed that fructose consumption led to hyperinsulinemia, glycogen synthesis stimulation and hypoglycemia, while stress did not influence the glucose metabolism. This indicates the existance of hepatic adaptive mechanisms, enabling it to keep the glucose homeostasis^[4],[5],[6]. Combined treatment was also followed by a visible lack of hepatic inflammation development and could be linked with the increased local glucocorticoid concentrations ^[7]. As part of this large study, we also showed that fructose enriched diet leads to an increase in the hepatic triglycerides and VLDL secretion consequent to the increased both hepatic and kidney de novo lipogenesis. Chronic stress showed no impact on the changes in the lipid metabolism, but it did cause an increase of hepatic de novo lipogenesis, followed by the increase of blood triglycerides and free fatty acids when combined with fructose consumption ^[8].

As far as female rats are concerned, we saw that the combination of fructose consumption and stress led to the increased prereceptor metabolism and GR-dependent glucocorticoid signalling. The same increase of nuclear GR concentration was seen in both individual treatments, as well. Fructose consumption increased the relative nuclear levels of the proadipogenic PPARγ together with an increased expression of main de novo lipogenic genes (FAS, ACC, PEPCK), thereby stimulating VAT adipogenesis. Stress itself increased the levels of HSL, decreasing VAT mass independently of the diet regime. Thus our results indicated that fructose consumption and chronic stress have antagonistic effects on the lipid metabolism of

[1] Bursać B, Djordjevic A, Veličković N, Milutinović DV, Petrović S, Teofilović A, Gligorovska L, Preitner F, Tappy L, Matić G. (2018) Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet. Mol Cell Endocrinol 476:110-118.

[2] Milutinović DV, Veličković N, Djordjevic A, Elaković I, Nestorov J, Bursać B, Teofilović A, Kovačević S, Nikolić M, Matić G. Interactions between stress and dietary fructose in the development of the metabolic-like phenotype in Wistar rat. 6th Swiss Winter Conference on Ingestive Behavior, Swiss Society for Nutrition, St. Moritz, Switzerland, February 28-March 5, 2015, pp. 22.

[3] Veličković N, Teofilović A, Djordjevic A, Milutinović DV, Bursać B, Nestorov J, Elaković I, Kovačević S, Gligorovska L, Nikolić M, Preitner F, Tappy L, Matić G. De novo lipogenesis and gluconeogenesis in the liver of male fructose-fed rats exposed to chronic stress. IUBMB Advanced School “Nutrition, Metabolism and Aging”, October 15-19, 2018, Petnica, Serbia, Book of abstracts, pp. 18

[4] Teofilović A, Brkljačić J, Djordjevic A, Milutinović DV, Tappy L, Matić G, Veličković N. (2020) Impact of insulin and glucocorticoid signalling on hepatic glucose homeostasis in the rat exposed to high-fructose diet and chronic stress. Int J Food Sci Nutr. DOI:10.1080/09637486.2020.1728236.

[5] Veličković N, Djordjevic A, Milutinović DV, Nestorov J, Elaković I, Teofilović A, Bursać B, Nikolić M, Kovačević S, Gligorovska L, Tappy L, Preitner F, Matić G. Effects of high-fructose diet and stress on hepatic metabolism in the Wistar rat: which is to blame? 13th Congress of Nutrition (CONU2016), Serbian Nutrition Society, Belgrade, Serbia, October 26-28, 2016, pp. 261-262.

[6] Teofilović A, Veličković N, Nestorov J, Bursać B, Djordjevic A, Milutinović DV, Elaković I, Preitner F, Tappy L, Matić G. Modulation of glucocorticoid and insulin signaling in the rat liver after high fructose diet and chronic stress. IUBMB Advanced School “Nutrition, Metabolism and Aging”, October 15-19, 2018, Petnica, Serbia, Book of abstracts, pp. 35

[7] Veličković N, Teofilović A, Ilić D, Djordjevic A, Milutinović DV, Petrović S, Preitner F, Tappy L, Matić G. (2018) Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high fructose diet and chronic stress. Eur J Nutr 58(5): 1829-1845.

[8] Milutinović DV, Brkljačić J, Teofilović A, Bursać B, Nikolić M, Gligorovska L, Kovačević S, Djordjevic A, Preitner F, Tappy L, Matić G, Veličković N. (2020) Chronic Stress Potentiates High Fructose–Induced Lipogenesis in Rat Liver and Kidney. Mol Nutr Food Res 64 (13): 1901141.