Author ORCID Identifier

https://orcid.org/0000-0001-7373-779X

Date of Graduation

8-2022

Document Type

Dissertation (PhD)

Program Affiliation

Biochemistry and Molecular Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Qingchun Tong, PhD

Committee Member

Ilya Levental, PhD

Committee Member

Kandice Levental, PhD

Committee Member

Vihang Narkar, PhD

Committee Member

Kartik Venkatachalam, PhD

Committee Member

Tryon Wickersham, PhD

Abstract

Metabolic disease and obesity affect millions of individuals worldwide and the prevalence of obesity is expected to continue to rise. Mechanisms underlying diet-induced metabolic disease and obesity are complex and are largely unknown. In this dissertation research, we aimed to make advances toward understanding how body temperature and high-fat diet consumption contribute to the development of obesity. Herein, we describe the progress that was made toward three research projects. In the first project, we develop novel animal models to determine the impact of reduced body temperature on obesity development and also demonstrate that severe obesity can be reversed through increased body temperature. In the second project, we evaluate a traditional, and widely used, model of high-fat diet-induced obesity and report critical findings that advance the knowledge of how and why obesity develops from high-fat diet consumption. We also report the impacts of high-fat diet consumption on the remodeling of the mammalian lipidome. Finally, in the third project, we generate two novel knock-in mouse strains, which can be utilized in future research to gain mechanistic insight into the causes of leptin resistance in obesity. Together, these three projects advance the understanding of how body temperature and diet drive obesity development and provide a rationale for future research geared towards the prevention and treatment of obesity.

Keywords

body temperature, diet, hypothalamus, leptin, leptin receptor, obesity

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