Diseases Commons^™

Western Diet-Like Culture Conditions And Oxidative Stress On A Cell Model Of Non-Alcoholic Fatty Liver Disease, Celina M. Valvano

Electronic Thesis and Dissertation Repository

Non-alcoholic fatty liver disease (NAFLD) is a major health burden in the Western world, as the Western diet (WD) appears to be the driving force of this disease. However, the individual contributions of the diet and the impacts of their individual metabolism are currently ill-defined. This study used HepG2 cells to understand the impact of the individual components of WD in early NAFLD development under basal insulin levels. Specifically, nutrient-induced changes in reactive oxygen species (ROS) and signaling pathways, such as sterol regulatory element binding proteins (SREBPs), were examined to identify the root cause of steatosis development. High-fat and WD-exposed …

The Effect Of Type 1 Diabetes On The Metabolic Response To Exercise, Theres Tijo

Undergraduate Student Research Internships Conference

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder that results in insufficient endogenous insulin production. Regular exercise has numerous health benefits for individuals with T1DM, however, most insulin-dependent diabetics avoid physical activity due to the fear of exercise-induced hypoglycemia (low blood glucose/BG).

The risk of hypoglycemia in this population may be partly due to lower liver glycogen stores which is a major source of blood glucose during exercise. However, the mechanism that leads to lower glycogen stores in T1DM is unknown.

The purpose of this study was to determine the effect of an acute bout of moderate-intensity aerobic exercise …

Advancing Type 2 Diabetes As A Condition For Primary Referral To Physiotherapy In Canada, Sarah M. Janssen

Electronic Thesis and Dissertation Repository

Obesity and sedentary lifestyle are increasingly prevalent risk factors for type 2 diabetes (T2D), characterized by high blood glucose levels. Adoption and maintenance of healthy eating, physical activity, and exercise is recommended for lowering blood glucose and weight management. Physiotherapists are experts in prescribing safe, effective exercise to optimize health for people with co-morbid health conditions. However, T2D is not a primary condition for referral to physiotherapy services in Canada. The overall question guiding a series of three related studies was, What is the current education and perspectives of Canadian physiotherapists about their role in managing T2D? Study one surveyed …

Increased Lipid Metabolism In Response To Repetitive Aerobic Exercise During Proestrus In Type 1 Diabetes Mellitus Rats, Silar Gardy

Electronic Thesis and Dissertation Repository

In response to repetitive bouts of aerobic exercise, type I diabetes mellitus (T1DM) female rats demonstrate greater post-exercise blood glucose (BG) recovery during proestrus than T1DM males. Fuel selection differences may explain sex-related differences in the blunted counterregulatory responses to subsequent exercise and estrogen (E2) has shown to mediate fuel metabolism. Evidence of E2’s activation of AMP-kinase (AMPK) may mediate the metabolic actions of E2. This study aimed to examine sex-related differences in lipid and glucose metabolism in response to a 4-day aerobic exercise protocol in skeletal muscle and liver tissue of male and female T1DM-induced (n = 5) and …

Mechanisms Underlying Enhanced Bone Marrow Adipogenesis In Diabetes, Jina J.Y. Kum

Electronic Thesis and Dissertation Repository

Morbidity and mortality associated with diabetes are due to secondary vascular complications that include both micro- and macro-vascular organ dysfunctions. Our recent studies show that vascular dysfunction and inadequate vessel repair in diabetes may potentially be due to impaired vasculogenesis (de novo vessel formation). Specifically, we have shown that diabetes enhances adipogenesis in the bone marrow and reduces the number of marrow-resident vascular regenerative stem cells. In this study, I have determined the mechanisms of deleterious bone marrow adipogenesis, which may alter the cellular composition of the marrow and lead to the depletion of vascular regenerative stem cells.

My …

The Effects Of Estrogen In The Glucoregulatory Response To Exercise In Type 1 Diabetes, Mitchell James Sammut

Undergraduate Student Research Internships Conference

Regular exercise has shown to benefit the health of individuals with type 1 diabetes mellitus (T1DM). However, a barrier to regular exercise for this population is the fear of low blood glucose (BG) levels, also known as hypoglycemia. Hypoglycemia can result in short and long-term side-effects, such as recurring loss of consciousness or in severe cases death.

In non-diabetics, sex-related differences in fuel selection during exercise are well established. Women shift towards using fats as fuel whereas men rely mostly on sugars (i.e., carbohydrates) for energy production. Exercise during the luteal phase of the female menstrual cycle, where estrogen levels …

The Effect Of Mtor Inhibitor Rapamycin On A Dietary Drosophila Melanogaster Model Of Calcium Oxalate Nephrolithiasis, Michael T. Pignanelli

Electronic Thesis and Dissertation Repository

Impaired cellular tolerance of reactive oxygen species (ROS) has been suggested as a common mechanistic link associated with aging in both metabolic syndrome and nephrolithiasis. The mechanistic (mammalian) target of rapamycin (mTOR) activity is characteristic of metabolic syndrome. When nutrients are abundant, mTOR is active. Conversely, fasting inhibits mTOR. Metabolic syndrome is correlated with an increased risk of self-reported or imaging findings of nephrolithiasis. At the individual level, patients with a higher BMI have an increased prevalence of recurrent symptomatic nephrolithiasis, 24-hour urinary excretion of oxalate, sodium, uric acid, calcium, and phosphorous as well as lower pH. Calcium oxalate crystals …

Optimizing Fecal Microbiota Transplantations For Therapeutic Use Beyond Clostridioides Difficile Infection, Laura J. Craven

Electronic Thesis and Dissertation Repository

Fecal microbiota transplantation (FMT) is an emerging and effective therapy for the treatment of recurrent Clostridioides difficile infection. Members of the gut microbiome have been implicated in other diseases and FMT has been considered as a potential therapy. Two such conditions include non-alcoholic fatty liver disease (NAFLD) and multiple sclerosis (MS), both of which involve increased small intestinal permeability believed to contribute to the development and disease progression. One of the aims of this project was to determine if FMT could be safely used in patients with NAFLD and MS to improve health outcomes. Before starting the clinical studies, optimal …

The Difference In A1c Of Children And Adolescents With Type 1 Diabetes Mellitus Using Carbohydrate Counting Compared To Those Using A Structured Meal Plan, Alia El Kubbe

Electronic Thesis and Dissertation Repository

Carbohydrate counting (CHO) is a nutrition education tool used by patients with type 1 diabetes mellitus (T1DM). The primary objective was to assess glycated hemoglobin (A1C) in participants with T1DM using CHO counting vs. those using a structured meal plan (SMP). The secondary objectives were to determine if BMI-for-age, parental income, parental involvement, and mothers’ educational level were associated with their children’s glycemic control. A cross sectional study was conducted, where participants aged 4-18 years, or their parents completed a survey. Total sample size was 88 participants (77 in the CHO counting group and 11 in the SMP group). There …

Effects Of Niacin And Vitamin D On Endothelial Cell Angiogenic Function And Vascular Regeneration During Lipotoxicity, Kia Mae Peters

Electronic Thesis and Dissertation Repository

Observational studies have suggested an association between low levels of niacin and vitamin D and increased cardiovascular disease risk. Both vitamins have been shown to improve endothelial functions and vascular regeneration following vascular injury, however, it appears vitamin D may promote or inhibit neovascularization in a context-dependent manner. We hypothesized that supplementation of vitamin D alone and in combination with niacin, would improve endothelial cell function under lipotoxic conditions and promote revascularization and functional recovery in obese mice with ischemic injury. Matrigel assays, mRNA microarray analyses and growth rate assays were used to investigate angiogenic function of endothelial cells exposed …

Parents As Agents Of Change In The Treatment Of Childhood Obesity And The Promotion Of Children's Health Behaviours, Kristen C. Reilly

Electronic Thesis and Dissertation Repository

The overarching purpose of this dissertation was to investigate the role of parents as agents of change in the treatment of childhood obesity and the promotion of children’s health behaviours. In order to achieve this purpose, four studies were conducted. The purpose of Study 1 was to explore parents’ perceptions of nutritional literacy, as well as their needs for nutritional literacy information, supports, and resources at familial and community levels. Next, Study 2 described the theoretical components and model used in the development and implementation of a parent-focused childhood overweight and obesity intervention (i.e., C.H.A.M.P. Families). The purpose of Study …

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, …

Metabolic And Expression Changes Associated With A Mouse Model Of Intrauterine Growth Restriction (Iugr), Bethany N. Radford

Electronic Thesis and Dissertation Repository

Intrauterine growth restriction (IUGR) is a pregnancy condition where fetal growth is suboptimal, resulting in an infant born small for gestational age (<10th percentile) and is associated with metabolic disorders such as type 2 diabetes in adulthood. This study aims to understand tissue-specific adaptations to fetal undernutrition which predispose the individual to metabolic disorders in adulthood. A model of growth restriction in mice was established using 70% of maternal ad libitum total food (g) (E6.5-birth). At weaning, male offspring received standard chow or a HFHS diet. Body weight and random blood glucose levels were measured at 6 months. To assess metabolism at 6 or 7 months, glucose tolerance, pyruvate challenge and hepatic portal vein insulin challenge tests were administered and serum peptide markers for obesity and diabetes were measured. Metabolic cages were also used at 2 and 7 months to measure activity, food intake and respiratory exchange ratios (RERs). Adult liver, adipose and skeletal muscle and fetal liver was collected for RNA sequencing. Maternal nutrient restricted (MNR) offspring were growth restricted with disproportionately smaller fetal livers. 19% of standard chow-fed MNR offspring became glucose intolerant. On an isocaloric high-fat high-sugar diet no differences in MNR growth or glucose metabolism were detected. However, RERs were reduced at all timepoints in MNR on a HFHS relative to MNR on standard chow. Differences in transcription of genes involved in hypoxia signalling were detected and HIF-2a and HIF-3a proteins were increased in fetal liver of MNR offspring. Genes differentially expressed in the fetus were not differentially expressed at 6 months. Gene expression of metabolically regulatory transcripts in liver, adipose and skeletal muscle did not differ in all MNR and glucose intolerant MNR relative to controls. This model results in a susceptible and non-susceptible population of maternal nutrient restricted offspring and supports the concept of hypoxia signalling contributing to fetal adaptations. Understanding adaptations in hepatic hypoxia signalling in response to fetal undernutrition and how they vary in susceptible and unsusceptible populations will provide insight into how fetal nutrition can influence adult metabolism.

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 …

Non-Invasive Determination Of Pre-Clinical Markers Of Cardiovascular Diseases In Low Birth Weight And Maternal Western Diet Guinea Pig Offspring Exposed To A Postnatal Western Diet, Jacky Chiu

Electronic Thesis and Dissertation Repository

Low birth weight (LBW), and maternal Western Diet (WD) consumption have both been independently implicated to increase the risk of developing cardiovascular diseases (CVDs) in later life. These fetal programmed risks are also believed to exacerbate the effects of a postnatal WD pattern. Therefore, resulting in the development of pre-clinical markers of CVDs, such as insulin resistance (IR), coronary circulation disruptions. This thesis aimed to elucidate the roles of sub-optimal in utero growth through placental insufficiency, or chronic maternal WD consumption, and postnatal WD consumption on the long-term programming of CVDs in a guinea pig model. Early pre-clinical markers of …

Molecular Mechanisms Linking Amino Acid (Leucine) Deprivation To Igfbp-1 Hyperphosphorylation In Fetal Growth Restriction, Niyati M. Malkani

Electronic Thesis and Dissertation Repository

In this study, we explore the molecular mechanisms linking amino acid (leucine) deprivation to IGFBP-1 hyperphosphorylation in vitro. During pregnancy, a maladaptive fetal response to in utero amino acid deprivation leads to Fetal Growth Restriction (FGR). FGR infants display elevated phosphorylated IGFBP-1, which is associated with decreased IGF-I bioavailability. Leucine deprivation inhibits mechanistic target of rapamycin (mTOR) signaling and stimulates the amino acid response (AAR). Using HepG2 cells, a model for fetal hepatocytes, we demonstrate that in leucine deprivation, the AAR modulates total and phosphorylated IGFBP-1 while mTOR mediates total IGFBP-1 secretion only. We also reveal that protein kinases …

Diabetic Bone Marrow & Stem Cell Dysfunction, Meghan A. Piccinin

Electronic Thesis and Dissertation Repository

ii Abstract Abstract Defects in the proliferation, differentiation, and activity of bone marrow (BM)-derived vasculogenic/vascular stem cells (VSCs) have been observed in diabetes and contribute to the development of vascular complications. Diabetes leads to enhanced bone marrow adipogenesis, altering the composition of the BM stem cell (SC) niche and potentially disrupting the normal functioning of resident VSCs. Here, I establish that adipocytes have a negative influence on SC survival in culture. I also show that adipocytes and osteoblasts are responsible for the creation of distinct extracellular microenvironments, with unique expression patterns of several pro- and anti-angiogenic factors with known effects …

The Effect Of Aerobic Exercise Training On Hepatic Glycogen Metabolism In Type 1 Diabetic Rats, Michael Murray

Electronic Thesis and Dissertation Repository

The purpose of this investigation was to determine if ten weeks of aerobic exercise training could increase hepatic glycogen storage in rats with Type 1 Diabetes Mellitus (T1DM) and whether elevated hepatic glycogen content is associated with alterations in glycogenic proteins and insulin signaling. Rats were divided into control-sedentary, control-exercised, T1DM-sedentary and T1DM-exercised groups. Animals from each group underwent a euglycemic-hyperinsulinemic clamp at the conclusion of the study. Exercise training consisted of treadmill running at 27m/min, 6% incline for 1hr, five days/week for ten weeks. T1DM rats had lower liver glycogen concentrations than control rats and glycogen was not increased …

Nerve Blood Flow Control In Health & Disease:The Effects Of Type 1 Diabetes And Exercise Training, Terry D. Olver

Electronic Thesis and Dissertation Repository

Peripheral nerve blood flow (NBF) is critical to nerve health. Impaired NBF control may contribute to the progression of diabetes peripheral neuropathy. The purposes of this dissertation were: i) to investigate the acute and chronic effects of hyperglycemia on basal sciatic NBF (measured via Doppler ultrasound), ii) to examine the potential vasodilatory effects of insulin (euglycemic hyperinsulinemic clamp; 10 mµ•kg^-1•min^-1) on NBF control in healthy rats and rats with insulin-treated type 1 diabetes (DS) and iii) to determine if exercise training (~75% VO₂max, 60 min/day, 5 days/wk for 10 wk) improves vasa nervorum reactivity …

Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal

Electronic Thesis and Dissertation Repository

Obstructive sleep apnea (OSA) is a chronic disorder involving repetitive interruptions in breathing during sleep. Sufferers of OSA are exposed to chronic intermittent hypoxia (CIH), characterized by cyclical reductions in oxygen availability. A number of studies have established a link between OSA and various cardiovascular and metabolic comorbidities in adulthood, including hypertension, obesity, and type II diabetes. While the consequences of OSA in adults have been well described, the cross-generational impact of this condition and potential effects on fetal development are not known. Epidemiological and animal studies have demonstrated that physiological insults during pregnancy lead to diminished growth of offspring …

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 …