UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
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 given thesis/dissertation in DRUM.
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Item The Role of Adipocyte Lipid Droplet Lipolysis in Thermogenesis and Metabolic Health(2017) Shin, Hyunsu; Yu, Liqing; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)My thesis was focused on the role of Comparative Gene Identification-58 (CGI-58)-mediated adipocyte lipid droplet (LD) lipolysis in thermogenesis and metabolic health. LD lipolysis in energy-dissipating brown adipose tissue (BAT) was believed to play a central role in cold-induced non-shivering thermogenesis, but this concept has not been tested in whole animal in vivo. We created a mouse line that lacks BAT CGI-58, a coactivator of Adipose Triglyceride Lipase (ATGL) that initiates the first step of cytosolic LD lipolysis by cleaving a fatty acyl chain from a triglyceride (TG) molecule. We found that BAT-specific CGI-58 knockout (BAT-KO) mice defend against the cold normally when food is absent, despite a defect in BAT LD lipolysis. Interestingly, BAT-KO versus control mice display higher body temperature when food is present during cold exposure. This cold adaptation in BAT-KO mice is associated with increases in BAT glucose uptake, insulin sensitivity, white adipose tissue (WAT) browning, energy expenditure, and sympathetic innervation. To identify the sources of fuels for thermogenesis of BAT-KO mice in the fasted state, we hypothesized that WAT lipolysis is a major source of thermogenic fuels during fasting. To test this hypothesis, we genetically inactivated CGI-58 expression in the whole fat tissues (both BAT and WAT) of mice (FAT-KO mice). We observed that FAT-KO mice are cold sensitive when food is absent, but tolerate cold normally when food is present, demonstrating that WAT lipolysis is essential for cold-induced thermogenesis during fasting and that dietary nutrients can substitute WAT lipolysis for fueling whole-body thermogenesis. Intriguingly, FAT-KO mice display a dramatic increase in cardiac glucose uptake under both basal and insulin-stimulated conditions, which is associated with significant increases in glucose tolerance, insulin sensitivity, and cardiac expression levels of natriuretic peptides. In conclusion, our studies demonstrate that 1) BAT LD lipolysis is not essential for cold-induced whole-body thermogenesis due to increased BAT uptake of circulating fuels and WAT browning; 2) WAT lipolysis is required for fueling thermogenesis during fasting; and 3) Adipose lipolysis is critically implicated in whole-body energy metabolism and cardiac function.Item Early Afterglow Evolution of X-Ray Flashes Observed by Swift(2006-03-08) Hullinger, Derek; Boldt, Elihu; Parsons, Ann; Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Gamma-ray bursts (GRBs) are bright flashes of gamma-ray energy that originate in distant galaxies and last only a matter of seconds before fading away, never to appear again. They are accompanied by longer-wavelength "afterglows" that fade away much more gradually and can be detected for up to several days or even weeks after the gamma-ray burst has vanished. In recent years, another phenomenon has been discovered that resembles gamma-ray bursts in almost every way, except that the radiated energy comes mostly from x-rays instead of gamma rays. This new class of bursts has been dubbed "x-ray flashes" (XRFs). There is strong evidence to suggest that GRBs and XRFs are closely-related phenomena. The Swift mission, launched in November of 2004, is designed to answer many questions about GRBs and their cousins, XRFs--where they come from, what causes them, and why gamma-ray bursts and x-ray flashes differ. The key to the Swift mission is its ability to detect and determine the location of a burst in the sky and then autonomously point x-ray and optical telescopes at the burst position within seconds of the detection. This allows the measurement of the afterglow within 1 - 2 minutes after the burst, rather than several hours later, as was necessary with past missions. This early afterglow measurement is an important key to distinguishing between different theories that seek to explain the differences between XRFs and GRBs. This dissertation describes the calibration of the Burst Alert Telescope, which measures the spectral and temporal properties of GRBs and XRFs. It also presents a study of XRFs and GRBs detected by Swift, including the first analysis and comparison of the early afterglow properties of these phenomena. This study reveals interesting differences between the temporal properties of GRB and XRF afterglows and sets strong constraints on some theories that seek to explain XRF origins.