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Exploratory study of egg white hydrolysate mechanisms of action in insulin sensitive tissues of high fat diet-induced insulin resistant rats
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- Author / Creator
- Zani, Stepheny
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Background: Chronic diseases related to the metabolic syndrome, such as type 2 diabetes and hypertension lead to complications when not treated properly. Natural approaches able to tackle multiple aspects of the metabolic syndrome and cause minimal side effects are desired. Bioactive peptides are short amino acid sequences that exert benefits beyond their nutritional value, improving health. Egg white is a rich source of bioactive peptides that are promising candidates as functional foods. Egg white peptides and hydrolysates (EWH) have been shown to reduce blood pressure, inflammation and fat mass, all related to the metabolic syndrome. Previously, feeding EWH for 6 weeks improved glucose and insulin tolerance in insulin resistant (IR) rats. Here, I aimed to identify EWH mechanism(s) of action related to glucose homeostasis. In this work I hypothesized that EWH supplementation affects multiple signaling pathways in insulin sensitive tissues to improve glucose tolerance in high fat diet (HFD)-induced insulin resistant rats.Methods: Sprague-Dawley rats were fed HFD for 6 weeks and then divided into 2 groups, HFD (n=7) and HFD+4% EWH (n=8) for another 6 weeks. 10 min prior to euthanization insulin was injected in half of the animals in each group. Insulin sensitive tissues (skeletal muscle, liver and white adipose tissue (WAT)) were tested, when applicable, for changes in insulin signalling, renin-angiotensin system (RAS) components, gluconeogenesis and lipolysis enzymes by western blot. In addition, WAT inflammatory markers and adipokines were measured by ELISA, PPARγ activation by DNA binding activity and adipocyte size by histological analysis. Results: EWH enhanced Akt phosphorylation in muscle and WAT of EWH-treated animals. RAS components abundance presented minimal changes, but notably there was increased angiotensin type 2 receptor (AT2R) in liver and WAT after EWH supplementation. The abundance of liver gluconeogenesis enzymes did not change. PPARγ DNA binding activity was enhanced and lipolytic capacity reduced by EWH in WAT. Moreover, the treatment reduced adipocyte size in epidydimal and retroperitoneal WAT, despite no changes in tissue inflammatory cytokines, resistin or adiponectin levels.Conclusion: In this study WAT was more responsive to EWH effects than other insulin sensitive tissues. In summary, the main findings of this study were that EWH changed adipocyte morphology, reduced adipocyte lipolytic capacity, enhanced insulin sensitivity in peripheral tissues, had little effect on local inflammation and induced only AT2R of the RAS components examined. The results are in accordance with our hypothesis showing that EWH is affecting insulin sensitive tissue to improve glucose tolerance through a variety of mechanisms and acts independently of changes in local inflammatory markers or adipokines. In WAT, a model linking EWH to AT2R activation, with downstream effects on PPARγ and Akt activation is proposed for further investigation. This research contributes to evidence for EWH as a potential product in the functional food market.
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- Graduation date
- Spring 2019
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.