Grant No. 152331

Fructose consumption and different daily stresses, as hallmarks of the modern lifestyle, are presently suspected to make a major contribution to the current epidemic of obesity and rising prevalence of metabolic syndrome, type 2 diabetes and coronary diseases. Since glucocorticoid hormones act antagonistically to insulin in maintenance of energy balance and play a vital role in systemic response to stress, we will study the contribution of glucocorticoid signaling alterations induced by chronic stress and/or fructose overconsumption to development of metabolic syndrome. Specifically, we will test the hypothesis that, in stressed animals, glucocorticoids will enhance fructose-induced stimulation of gluconeogenesis and de novo lipogenesis and will decrease fructose-induced lactate production. The study will be performed on an animal model of metabolic syndrome, obtained by exposure of male and female rats to 9-week fructose-enriched diet and/or chronic unpredictable stress. Validation of the animal model will be performed by measuring a number of biochemical and physiological parameters. The level of expression of the enzymes and transcription regulators of interest will be assessed by qPCR, Western blotting and ELISA, as appropriate. Lipid and carbohydrate metabolic pathways in the liver and adipose tissue will be quantified by using stable isotope-labeled metabolic precursors in combination with gas chromatography-mass spectrometry and mass isotopomer distribution analysis. The proposed project is expected to make a breakthrough in fundamental knowledge on the interaction of stress and dietary fructose in glucocorticoid signaling alterations and development of metabolic syndrome, as well as on sex-related differences in vulnerability to metabolic syndrome. The project will be conducted through collaboration between the project partners from the University of Lausanne and University of Belgrade. It will promote the exchange of know-how and ensure transfer of stable isotope-labeling technology from the Swiss team to Serbian researchers, thus significantly improving research performance of the Serbian partner.

Period: 2014-2017

Coordinator: Dr. Gordana Matić