Medicine and Health Sciences Commons^™

Effects Of Ergothioneine On Endothelial Cell And Macrophage Characteristics, And Markers Of Atherosclerosis Risk Under High Lipid Conditions, Daniel Lam-Sidun

Electronic Thesis and Dissertation Repository

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 …

Attenuation Of Obesity, Hepatic Steatosis And Reversal Of Atherosclerosis By The Flavonoids Naringenin And Nobiletin, Amy C. Burke

Electronic Thesis and Dissertation Repository

Naringenin and nobiletin are naturally-derived citrus flavonoids that have significant lipid-lowering and insulin sensitizing effects in vitro and in vivo. In murine models of obesity, metabolic dysfunction and atherogenesis, these flavonoids protect against the development of cardiometabolic disease. However, the ability of naringenin and nobiletin to reverse existing metabolic dysfunction and atherosclerosis has not been investigated.

The purpose of this thesis was to investigate the ability of the citrus flavonoids, naringenin and nobiletin, to reverse obesity, metabolic syndrome and atherosclerosis in two different mouse models of atherosclerosis regression. The first chapter demonstrates in Ldlr^-/- mice with diet-induced obesity, …

Panx1 And Panx3 Regulate Adipocyte Development And Fat Accumulation In Vivo, Vanessa R. Lee

Electronic Thesis and Dissertation Repository

The obesity epidemic is a growing concern due to its various comorbidities and associated risk factors. Pannexins 1 and 3 (Panx1 and Panx3), are members of a family of channel-forming glycoproteins that have been reported to be important in paracrine signaling and development. Panx1 and Panx3 are homologous and are regulated in many different cell types, mediating cell proliferation and differentiation. We have shown that Panx1 and Panx3 are expressed in adipocytes and adipose-derived stromal cells (ASCs) throughout the process of differentiation. Mice globally lacking Panx1 (Panx1 KO) have significantly greater total fat mass compared to wildtype (WT) mice under …

A Link Between Paediatric Asthma And Obesity: Are They Caused By The Same Environmental Conditions?, Phylicia Gonsalves

Electronic Thesis and Dissertation Repository

The highly associated paediatric conditions of asthma and overweight have seen dramatic increases over the past few decades. This thesis explored air pollution exposure as a potential underlying mechanism of co-morbid asthma and overweight among adolescents aged 12 to 18 years. Data from the Canadian Community Health Survey were merged with a database containing estimates of air pollution as assessed by particulate matter ≤ 2.5 microns (PM_2.5) concentrations at the postal code centroid in southwestern Ontario. Logistic regression was used to conduct the analysis. Adolescents were more likely to be overweight as PM_2.5 concentrations increased. There was …

Effects Of Niacin In Human Vascular Endothelial Cells During Lipotoxicity, Jennifer M. Hughes-Large

Electronic Thesis and Dissertation Repository

Nicotinic acid (NA) can improve vascular function and regeneration independent of correcting dyslipidemia. NA, as a potential biosynthetic precursor for NAD⁺, may elicit these vascular benefits through SIRT-mediated NAD⁺-dependent responses. We hypothesized that NA improves endothelial cell function under lipotoxic conditions through NAD⁺-dependent pathways. Angiogenic function in excess palmitate was assessed by tube formation assay following treatment of human microvascular endothelial cells (HMVEC) with NA or nicotinamide mononucleotide (NMN; a direct NAD⁺ precursor). Both NA and NMN improved HMVEC angiogenic function during palmitate overload. Only NMN increased cellular NAD⁺ and SIRT1 activity, …

Elongation Factor 1a-1 And Hepatocyte Response To Fatty Acid Excess, Alexandra M. Stoianov

Electronic Thesis and Dissertation Repository

Obesity is associated with elevated levels of serum fatty acids, which accumulate in nonadipose tissues including the liver. Elongation factor 1A-1 (EF1A-1) has previously been shown to participate in the cell stress and death response of cardiomyocytes to excess saturated fatty exposure, and in steatotic mouse myocardium. In this thesis, the hypothesis that the hepatocyte response to fatty acid overload involves EF1A-1 was tested. EF1A-1 expression was induced in the livers of obese mice in association with severe hepatic steatosis, and in HepG2 human hepatoma cells in response to excess palmitate. Partial translocation of EF1A-1 from the ER to polymerized …