Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Borradaile, Nica M

Abstract

Ergothioneine (EGT) is an antioxidant and potential anti-inflammatory molecule that may have protective effects against the lipid-induced oxidative stress and inflammation that occurs in the vasculature of individuals with obesity and metabolic syndrome. This thesis addresses the hypothesis that EGT supplementation decreases endothelial cell dysfunction and macrophage inflammatory characteristics under high lipid conditions, and markers of atherosclerotic risk in diet-induced obese mice. Results showed that EGT did not influence endothelial tube formation or stability but reduced nitric oxide production in endothelial cells. Moreover, EGT decreased the production of reactive oxygen species, and potentially nitric oxide, by macrophages. In diet-induced obese mice with characteristics of metabolic syndrome, EGT did not influence circulating lipid, lipoprotein and glucose concentrations which are markers of atherosclerotic risk. In conclusion, EGT has moderate effects on vascular cells in vitro, and does not influence blood glucose and lipid markers of vascular disease risk in diet-induced obese mice.

Summary for Lay Audience

Obesity is a chronic disease that puts individuals at risk for metabolic syndrome. Those diagnosed with metabolic syndrome have high levels of fats and sugar in their bloodstream, which can deposit in cells and tissues throughout the body and cause oxidative damage. Endothelial cells, which line the inner walls of blood vessels, are vulnerable to injury from these high levels of circulating fats and sugar. In addition, immune cells such as macrophages, which also circulate in the bloodstream, can accumulate excess fats, and drive chronic inflammation within blood vessel walls. As a result of both endothelial cell damage and chronic inflammation in blood vessels, vascular disease can develop. Atherosclerosis, a vascular disease, is a condition characterized by the build up of fat in blood vessel walls leading to blockages and decreased blood flow to tissues and organs which can result in heart attacks and strokes. Ergothioneine (EGT) is an antioxidant and potential anti-inflammatory molecule that may be a potential candidate to help protect against blood vessel cell stress induced by high fat. EGT is specifically found in mushrooms and there is some evidence that EGT may modify vascular disease risk by altering fat levels in the bloodstream and protecting cells against oxidative damage. This project investigated whether EGT supplementation could modify vascular disease risk under high fat conditions. EGT was shown to have moderate effects on endothelial cell and macrophage function during exposure to high fat conditions in petri dishes. Further studies in obese mice fed a high fat diet revealed no effects on body weight or characteristics of metabolic syndrome (blood fats and sugar) as markers of atherosclerosis and vascular disease risk. It is possible that the dose and duration of EGT supplementation given to obese mice were not high enough or long enough to cause significant changes in the characteristics of metabolic syndrome which increase vascular disease risk. Future studies will determine whether EGT could be used as a vascular health supplement for individuals with obesity and metabolic syndrome.

Creative Commons License

Creative Commons Attribution-Share Alike 4.0 License
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 License.

Available for download on Wednesday, August 30, 2023

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