Date of Award

2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Sigrid C. Veasey

Second Advisor

Allan I. Pack

Abstract

Obesity is associated with numerous metabolic and behavioral abnormalities, including excessive daytime sleepiness independent of sleep disorders (e.g., sleep apnea). In humans, obesity is traditionally classified by weight metrics such as body mass index (BMI); over one-third of Americans are obese based on BMI. The most common cause of obesity is chronic positive energy balance due to overconsumption of calorically-dense diets. However, it is difficult to isolate the independent effects of ‘overnutrition/positive energy balance’ and ‘excess body weight’ on metabolic and behavioral parameters since the former causes the latter. Therefore, the focus of this dissertation is to discover how diet/energy balance, independent from body weight, affect sleep/wake behavior and metabolic health using the high-fat diet (HFD)-induced obese mouse model. In Chapter 2, I introduce the Diet Switch (DS) feeding paradigm which generates two groups of mice of similar body weight by divergent energy balance. Using the DS protocol, I show that diet-induced changes to energy balance can affect sleep and wakefulness independent of actual body weight. In Chapter 3, I explore the role of a central regulator of energy balance, peroxisome proliferator-activated receptor gamma (PPARg), on HFD-induced sleep abnormalities; our results indicate that central PPARg does not influence sleep/wake behavior. In Chapter 4, I again use the DS feeding paradigm, but instead measure various molecular (blood biomarkers and hypothalamic gene expression), behavioral (spontaneous activity), and metabolic (indirect calorimetry) outcomes. Using linear regression modeling, I quantify the relative influence of body weight and diet/energy balance on these parameters, and relate these key findings to the results from Chapter 2. Taken together, these studies offer novel insights into the pathogenesis and reversibility of obesity-related sleep and metabolic disorders.

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