Masters Degrees (Physiological Sciences)

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Browsing Masters Degrees (Physiological Sciences) by Author "Benade, Janina"

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    Are early proteomic and metabolic changes induced by long-term sugar-sweetened beverage consumption the key to unlocking the cardio-metabolic pandemic?
    (Stellenbosch : Stellenbosch University, 2017-03) Benade, Janina; Essop, M. Faadiel; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: INTRODUCTION: Cardio-metabolic diseases (e.g. type 2 diabetes mellitus) are a major cause of mortality worldwide. The incidence of cardio-metabolic diseases continues to increase, especially in low and middle income countries. This “pandemic” is possibly brought about by a fairly universal shift towards a more “Westernized” diet. High sugar consumption - a hallmark of the “Westernized” diet - may play a key role in the onset of cardio-metabolic diseases. Accordingly, our research focus moved towards sugar-sweetened beverages (SSBs) as it is a major source of added dietary sugars. The current study aimed to elucidate underlying mechanisms leading to the development of cardiometabolic diseases by exploiting a novel rat model of long-term SSB intake, and by focusing on the liver as a major metabolic organ. Here we evaluated well-known systemic markers together with hepatic proteome analysis and downstream consequences. METHODS: Male Wistar rats ( 200 g) were gavaged with 3-5.1 mL SSB daily for three and six months, respectively. The two control groups were gavaged with an iso-volumetric amount of water and iso-caloric amount of butter, respectively. Body weight and systemic blood markers were measured. A proteomic expression analysis was performed on the six-month liver samples. The rest of our experimental work was guided by the proteomic results. Four markers for oxidative stress were evaluated: malondialdehyde, conjugated dienes, reduced:oxidized glutathioneand oxygen radical absorbance capacity. The non-oxidative glucose pathways (NOGPs): polyol pathway, hexosamine biosynthetic pathway, advanced glycation end-products formation and protein kinase C activation; were measured as elevated activity could be indicative of impaired glycolytic flux. The liver histology was investigated with Hematoxylin and Eosin and Masson’s Trichrome stains, respectively. Finally, Western blotting techniques were used to evaluate markers of inflammation. RESULTS: SSB consumption had little effect on systemic markers of cardio-metabolic health. Our proteomic analysis revealed that the expression level of 140 proteins was significantly altered in the SSB group, with a major finding that SSB consumption induces hepatic endoplasmic reticulum (ER) stress. Initially the liver adapted to SSB-mediated nutrient overload by increasing oxidative phosphorylation, suppressing protein transcription, degrading misfolded proteins and improving protein folding capacity. However, due to prolonged stress liver cells entered an ‘’alarm phase’’ marked by a decrease in mitocholdrial metabolism. The proteomic results further revealed that SSB-induced effects are largely attributed to excess caloric intake versus SSBs per se. Surprisingly, oxidative stress did not precede ER stress as there were no significant changes in any of the oxidative stress markers here evaluated. The activity of the NOGPs did not increase significantly thus suggesting that moderate SSB intake did not suppress glucose metabolism and the glycolytic pathway in particular. Conversely, SSB intake increased hepatic lipid storage while limited changes were detected between the groups regarding inflammation and stress signaling. CONCLUSION: Frequent SSB consumption triggers metabolic changes in the liver, i.e. ER stress despite the lack of obvious manifestation of macroscopic “warning signs”. Thus the current study identifies hepatic ER stress as a relatively early result of long-term SSB consumption and it therefore emerges as a unique therapeutic target.