Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item O-GLCNACYLATION IS NOT INCREASED IN THE HYPOTHALAMUS OF RATS GIVEN 6 WEEK ACCESS TO SUCROSE SOLUTION DESPITE MARKERS OF METABOLIC DYSREGULATION(2018) Hudgins, Samantha Morgan; Castonguay, Thomas W; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The peptide hormone leptin acts globally to maintain various metabolic processes. Impaired response to leptin binding is referred to as leptin resistance and results in metabolic dysregulation. Leptin is essential in the prevention of weight gain through central signals to increase energy expenditure and reduce food intake. A sugar sensitive pathway, the hexosamine biosynthesis pathway (HBP), may be the cause of diet induced leptin resistance. The HBP glycosylates proteins by modifying fructose- 6-phosphate molecules from glycolysis. While high sugar diets have been linked to leptin resistance, O-GlcNAcylation of pathway proteins have not been examined. Approximately 8-week-old male rats were assigned to ad libitum access to diet and water or 30% sucrose solution, diet and water. On Day 5 rats were surgically fitted with a third ventricle cannula. On Day 41, diet and sugar solutions were removed for an overnight fast. On Day 42 each rat received a central injection of leptin or control solution and subsequently euthanized 30 minutes post injection. Body weight and body composition were not significantly different between treatment groups after 42 days. However, the Sucrose group exhibited signs of metabolic syndrome, evidenced by increased fasting serum triglycerides and glucose as well as decreased serum HDL. Analysis of hypothalamic O-GlcNAcylation revealed no significant difference between treatment groups. These data may be the result of variability of glucose utilization within the hypothalamus. These data support previous findings that 42-day access to a 30% sucrose solution yields evidence of metabolic syndrome in the absence of obesity as well as the absence of increased hypothalamic OGlcNAcylation. Future research should examine O-GlcNAcylation regionally within the hypothalamus. Analysis of protein specific O-GlcNAcylation was not achieved; however, a novel O-GlcNAcylation was observed in hypothalamic tissue at the Threonine 1808 residue of prolow-density lipoprotein receptor-related protein 1 isoform X1 (LRP-1), a protein that may play a crucial role in leptin signaling. These data give further evidence to support the use of 30% sucrose solution to model leptin resistance in Sprague Dawley rats, as well as provide a target protein for future analysis.Item Appetite signals in the brain: High fructose corn syrup sweetened cola effects hypothalamic activity as measured by functional magnetic resonance imaging(2014) Hudgins, Samantha Morgan; Castonguay, Thomas W; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Functional Magnetic Resonance Imaging has been used for over a decade to measure the effects of sugar on the hypothalamus, the appetite-regulating center of the brain. Hypothalamic activity decreases in a dose-dependent manner in response to glucose solution consumption. Fructose elicits an increase in hypothalamic activity. This study aimed to understand the effects of high fructose corn syrup, a combination of glucose and fructose on hypothalamic activity. Fasting blood samples were collected from 8 (4M /4F) healthy adult volunteers who were then fed a standard breakfast and transported to the Maryland Neuroimaging Center. Participants underwent two successive scans. Prior to the first scan participants drank 12 oz. of either cola or water. After the first scan participants received 6 oz. of either cola or water immediately prior to the beginning of the second scan. Treatments were assigned in a Latin square crossover design. Each scan included ~17mins of T2 weighted functional scanning of the hypothalamus (12 mm mid-sagittal slice; echo time: 5ms; repetition time 40ms; flip angle: 40°; FOV: 210 mm; in-plane resolution: 1.6mm X 1.6mm). MANOVA revealed a statistically significant three-way interaction between time, volume and treatment when the model was weighted with either fasting insulin (p<0.0001) or fasting triglycerides (p=0.023). Gender also significantly interacted with time, volume and treatment (p=0.008). Further, age was negatively correlated with overall average hypothalamic signal intensity with volume as well with treatments. Both demographics and metabolites strongly influence hypothalamic response, making it difficult to determine the specific effects of high fructose corn syrup sweetened cola on appetite signals in the hypothalamus.