Author ORCID Identifier
Semester
Fall
Date of Graduation
2024
Document Type
Dissertation
Degree Type
PhD
College
School of Medicine
Department
Biochemistry
Committee Chair
Michael Gunther
Committee Co-Chair
Eric Kelley
Committee Member
Roberta Leonardi
Committee Member
Valery Khramtsov
Committee Member
Robert O'Doherty
Abstract
Uric acid (UA) is the single most tightly associated metabolite for obesity and type 2 diabetes. While the field varies on whether UA is causative or correlative of the metabolic dysfunction allied to obesity, these studies use different diets and animal models to make these claims. It is the goal of this dissertation to compare different diets commonly used in this research to delve deeper into the data and determine which diets induce elevated circulating UA levels as well as which diets also induce metabolic dysfunction. Early chapters of this dissertation examine the comparison of high fructose consumption, both in the diet and drinking water, to high fat diets, while also using a hepatocellular-specific knockout of Xdh to determine if it can prevent the previously described results of a NASHogenic diet. The published work of a side-by-side comparison of males and females on the 60% high fat diet shows that while female mice are slightly more resistant to the effects of the diet at early time points, leading to less impairment of glucose tolerance and a delay in weight gain. However, by the end of 19 weeks on the diet, there is very little difference in the metabolic outcomes between the sexes and they both are hyperuricemic which is the first fully conclusive report of female murine hyperuricemia in response to obesogenic feeding. Further work compared the 60% high fat diet to a custom diet made to mimic the consumption of West Virginians that present to the clinic for obesity related diseases, providing evidence that while consumption of the diets did not result in any differences in UA levels, the diets did play a significant role in the type of metabolic abnormalities experienced. Specifically, the 60% high fat diet led to greater impairment of glucose tolerance while the WV-HFD led to greater elevation of circulating cholesterol and triglycerides. When taken together, this body of work has moved the field forward by revealing several important details regarding diets, obesity, sex and metabolic responses.
Recommended Citation
Giromini, Andrew P., "The Role of Uric Acid in Metabolic Abnormalities of Obesity" (2024). Graduate Theses, Dissertations, and Problem Reports. 12654.
https://researchrepository.wvu.edu/etd/12654