Date of Award

Fall 2021

Document Type

Open Access Dissertation

Department

Biomedical Science

First Advisor

Reilly Enos

Abstract

Menopause puts a female at risk for several chronic diseases, including an increased risk of obesity. Estrogens are major sex hormones of females that dramatically decrease during menopause. Several murine studies have established the crucial role of estrogen and estrogen receptor alpha (ERα) on energy homeostasis, glucose metabolism, and insulin action. However, previous works have produced contradicting findings, hence, further work is needed to optimize better outcomes. Therefore, my dissertation focuses on optimizing and characterizing different estrogen-deficient models, as well as using novel double transgenic inducible and tissue-specific models that overexpress aromatase (estrogen producing enzyme) and estrogen receptor isomers alpha (ERα) in the skeletal muscle of female mice. Using the aromatase knock out (Arom KO) model, data analysis revealed that estrogen deficiency increases adiposity primarily via decreasing of physical activity rather than changes in food intake. Also, skeletal muscle ERα, protects female mice against obesity and metabolic dysregulation independent of the estrogen status. On the other hand, skeletal muscle aromatase overexpression limits adipose tissue inflammation, however, no impact on adiposity or metabolic dysregulation were observed. This work presents, for the first time, differing effects of estrogen manipulating models on the development of the obese phenotype in the females. Inducible transgenic model in this work can be utilized to overexpress/delete ERα in different metabolic tissues for better understanding estrogen action on metabolism.

Rights

© 2021, Ahmed Aladhami

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