Date of Graduation

Summer 2023

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Randi Ulbricht

Abstract

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of a cytoplasmic RNA sensor, MDA-5. While MDA-5 expression is sex-dependent, differences in ADAR1 levels are unexplored. To look at how inflammation affects ADAR1 expression was measured from male and female mice injected with lipopolysaccharide (LPS), an agent known to cause inflammation. In order to look at the sex-dependent effects of inflammation on physiology, glucose tolerance tests were also done in LPS treated mice. Mice treated with LPS showed increased levels of ADAR1 and cytokines, as expected. There was also a sex-dependent effect on glucose tolerance, where inflammation affected blood glucose levels to a greater extent in male inflamed mice, compared to control males, or any female mice. The data suggests that inflammation induces insulin resistance in a sex-dependent manner and that female mice are protected from inflammation-dependent changes in glucose tolerance. We anticipate this information will help us understand sex-disparities in inflammatory-related disease progression and outcome.

Keywords

RNA editing, LPS, innate immunity, glucose tolerance testing, glucose metabolism, lipopolysaccharide, immunity, ADAR1, ADAR1p150, research

Subject Categories

Cell Biology | Cellular and Molecular Physiology | Endocrine System | Endocrinology | Immunity | Immunopathology | Laboratory and Basic Science Research | Molecular Biology | Organismal Biological Physiology

Copyright

© Christian A. Rivas

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Open Access

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