This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.My long-term goal is to develop an independent career as a translational researcher, bridging the gap between basic science applications and clinical research. My current work is funded by a K-23 award from the NIH and a new resource at UT Southwestern, the Disease-Oriented Clinical Scientist program. I am interested in the epidemiology and metabolic basis of non-alcoholic fatty liver disease (NAFLD), with a special interest in the ethnic disparities that exist with this disease. Under the mentorship of Jay D. Horton, M.D. and Craig Malloy, M.D., I will investigate the metabolic basis of NAFLD. Virtually nothing is known about the fluxes in hepatic glucose production pathways in the setting of dietary carbohydrate-restriction or excess. The liver is the central governor of whole-body fuel metabolism, modulating fuel availability in the form of glucose, ketones, and fatty acids. Under normal conditions, the liver can adapt to different situations (starvation, malnutrition, exercise) and maintain the delivery of energy-rich substrates to the periphery that exactly meet demand. However, obesity and insulin resistance can lead to a derangement in hepatic metabolism typified by increased glucose production, enhanced de novo lipogenesis, and decreased oxidation of already abundant fatty acids. This can result in the typical phenotype of fasting hyperglycemia, elevated triglycerides, and hepatic steatosis. Current dietary recommendations for both weight loss and diabetes mellitus espouse the use of a high-carbohydrate diet with little data regarding the effect of this diet on hepatic metabolism. This work relies on two different features of the RR: the expertise and instrumentation for 2H and 13C NMR isotopomer analysis, and access to the high field human imaging and spectroscopy equipment.
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