@phdthesis{
author = "Kovačević, Sanja",
year = "2017",
abstract = "Savremen način života karakterišu prekomeran unos fruktoze i svakodnevni stres koji koincidiraju sa pojavom metaboličkog sindroma (MetS), vodećeg faktora rizika za razvoj dijabetesa tipa 2 i bolesti srca. Narušen signalni put glukokortikoidnih hormona (GH), regulatora metabolizma i odgovora na stres, može biti uključen u patofiziologiju MetS-a.
Cilj ove doktorske disertacije bio je da se testira hipoteza da fruktoza u kombinaciji sa hroničnim stresom dovodi do poremećaja u signalnom putu GH odgovornih za razvoj karakteristika MetS-a kod ženki pacova. U tom cilju ispitani su efekti devetonedeljnog izlaganja ishrani obogaćenoj fruktozom i nepredvidivom stresu na prereceptorski metabolizam GH, ekspresiju i funkciju glukokortikoidnog receptora i njime regulisanih gena uključenih u metabolizam masti u visceralnom masnom tkivu (VMT). Pod istim uslovima ispitani su i leptinski signalni put u hipotalamusu i inflamatorni status oba pomenuta tkiva.
Rezultati pokazuju da dugoročna ishrana obogaćena fruktozom stimuliše adipogenezu i de novo lipogenezu u VMT-u, dok hronični nepredvidivi stres promoviše lipolizu. Iako suprotni, ovi efekti su najverovatnije posledica aktivnosti GH. Nijedan od tretmana nije uticao na leptinski signalni put niti na regulaciju unosa hrane u hipotalamusu. Takođe, rezultati sugerišu da je inflamacija u VMT-u jedna od prvih posledica konzumiranja fruktoze budući da se razvija pre nego što se mogu uočiti gojaznost i inflamacija u hipotalamusu.
Sumarno, fruktoza svojim lipogenim uticajem uzrokuje metaboličke i fiziološke promene koje doprinose razvoju metaboličkog sindroma, dok su posledice hroničnog stresa izraženije u odnosu na efekte fruktoze i predominantno usmeravaju metabolizam ka potrošnji energije, pri čemu u oba slučaja GH ostvaruju značajan doprinos., Hallmarks of modern lifestyle, fructose overconsumption and daily exposure to unpredictable stress, coincide with the onset of metabolic syndrome (MetS), leading risk factor for the development of type 2 diabetes and cardiovascular diseases. Glucocorticoid hormones (GC), main regulators of metabolism and response to stress, could be involved in the pathophysiology of MetS.
The aim of this doctoral dissertation was to test the hypothesis that the combination of fructose diet and chronic unpredictable stress evokes disturbances in GC signaling responsible for the development of MetS in female rats. We analyzed the effects of 9 week exposure to fructose enriched diet and stress on GC prereceptor metabolism, expression and function of glucocorticoid receptor and receptor regulated genes involved in lipid metabolism in visceral adipose tissue (VAT). Also, we analyzed leptin signaling in hypothalamus and inflammation in both tissues.
Results showed that long term fructose overconsumption stimulated adipogenesis and de novo lipogenesis in VAT, while chronic stress promoted lipolysis. Although opposing, these effects probably result from the GC activity. Leptin signaling and appetite regulation in hypothalamus were not affected by these treatments. Also, results suggest that VAT inflammation is one of the first consequences of fructose overconsumption as it was developed before the onset of obesity and inflammation in hypothalamus.
In summary, lipogenic effects of fructose elicit metabolic and physiologic disturbances that contribute to the development of MetS, while chronic stress predominantly directs metabolism to energy expenditure and exceeds the effects of fructose. In both cases, GC play a significant role.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Razvoj metaboličkog sindroma izazvanog kombinacijom stresa i ishrane obogaćene fruktozom - doprinos glukokortikoida u visceralnom masnom tkivu i hipotalamusu ženke pacova, The development of metabolic syndrome induced by the combination of stress and fructose enriched diet – the contribution of glucocorticoids in visceral adipose tissue and hypothalamus of female rats",
pages = "1-162",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2850"
}
