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 Regulation of Mitochondrial Metabolism and Lipogenesis(2021) Surugihalli, Chaitra; Sunny, Nishanth E; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Non-alcoholic fatty liver disease is one of the most common liver disorders with a global prevalence of over 25%. Fatty liver is the most common comorbidity of insulin resistance, obesity, and type 2 diabetes mellitus. During fatty liver, nutrient overload and the associated hyperinsulinemia results in elevated circulating free fatty acids and lipid accumulation in the liver. High rates of lipid accumulation in the liver is partly attributed to high rates of lipogenesis from carbohydrates, together with dysfunctional lipid oxidation. Further, these dysfunctional metabolic networks will induce oxidative stress and inflammation. Thus, understanding the metabolic mechanisms contributing towards the etiology of fatty liver and its associated morbidities is of major interest towards developing prevention and management strategies. This dissertation utilizes a combination of in-vivo (chicken and mice) and in-vitro (isolated mitochondria) systems with stable isotope-based methodologies to study metabolic regulation.Chicken embryos utilize yolk lipids (>45%), deriving over 90% of their energy through lipid oxidation for development. However, during the last few days of incubation and immediately after hatch, there is a substantial induction of lipogenesis. Despite the hepatic lipid overload, the synergistic remodeling of hepatic metabolic networks during embryonic-to-neonatal development blunted inflammatory onset, prevented accumulation of lipotoxic intermediates, and reduced reactive oxygen species production. Elevated plasma branched-chain amino acids (BCAAs) are a characteristic of insulin resistance and are relevant in predicting T2DM. Defects in BCAA degradation networks are also evident in several tissues during insulin resistance and associated co-morbidities. Furthermore, alterations in BCAA metabolism are associated with changes in lipogenesis and mitochondrial oxidative networks. We utilize a combination of isolated mitochondrial systems and stable isotope tracers in diet-induced mouse models of fatty liver, to determine its impact on mitochondrial metabolism and lipogenesis. In summary, the dissertation highlights i) the importance of the natural but dynamic remodeling of hepatic mitochondrial metabolism and lipogenesis during the efficient embryonic-to-neonatal transition in chicken ii) the significance of BCAAs as important regulators of hepatic mitochondrial lipid metabolism. Thus, these studies provide a platform to modulate hepatic metabolic networks and utilize the embryonic-to-neonatal transition phase and dietary intervention of BCAAs as management strategies to alleviate metabolic dysfunctions.Item THE EFFECTS OF SUGAR INTAKE ON ENERGY CONTROL(2015) Zhao, Changhui; Castonguay, Thomas W; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Long term use of sugars can induce excess caloric intake and/or obesity. To evaluate the effects of sugar intake on different regions of the hypothalamus (the brain's control center for energy homeostasis) we first developed and then evaluated a microscope-assisted dissection method. Because of the small size of the paraventricular nucleus, we validated the samples by measuring several hormones mainly synthesized in the paraventricular nucleus. These include corticotropin-releasing hormone, oxytocin, arginine vasopressin and thyrotropin releasing hormone. We measured the mRNA expression of each of these hormones using quantitative PCR and detected them principally in the paraventricular nucleus. We further evaluated the effects of various sugar solutions on the expression of several important hypothalamic neuropeptides because they play a pivotal role in energy homeostasis. We provided Sprague Dawley rats 24 hour access to 15% solutions of glucose, fructose, sucrose or high fructose corn syrup. We then measured the expression of several neuropeptides in different hypothalamic regions, all of which were previously shown to be influenced by sugar consumption (mainly based on the results from a series of PCR arrays). Additionally, we measured plasma leptin, known for its close correlation with body fat mass. As expected, rats that had access to sugar solutions consumed less chow. However, rats with free access to sugar solutions maintained a similar amount of energy intake compared with control. Of the four sugars tested, only fructose decreased expression of cholecystokinin significantly, whereas glucose and sucrose significantly increased the expression of tumor necrosis α only in the paraventricular nucleus, not in the ventromedial nucleus or the lateral hypothalamic area. Fructose and sucrose decreased growth hormone expression in the ventromedial nucleus. Glucose increased dopamine receptor D1A expression in the paraventricular nucleus only. We conclude that 24 hour free access to different sugars can influence the expression of several hypothalamic neuropeptides in different ways and these changes are region dependent. Changes in the expression of these neuropeptides do not disrupt the total energy intake immediately but may contribute to the obesity caused by long term intake of sugars.