My long-term professional goal is to become a successful, independent scientist with a research program
focused on obesity and the neurobiological regulation of feeding and activity in response to exercise. Obesity
continues to be a major health concern and obesity risk is increased with exposure to early life stress.
Exposure to early life stress is very common in the United States and yet we do not fully understand how early
stress alters reward neurocircuitry to affect the motivation to consume palatable foods and be physically active.
The reward system control of body weight relies on the inherently rewarding value of foods, particularly those
high in fat and sugar, and of physical activity. Within the brain, the motivation to obtain these natural rewards is
driven by dopaminergic activity in the nucleus accumbens (NAc) and ventral tegmental area (VTA).
Glucocorticoid receptors are found throughout reward regions of the brain and chronic hypercorticosteronemia,
such as that associated with early life stress exposure, has been shown to inhibit dopamine release and
turnover in the NAc. Additionally, one of the greatest issues facing individuals with obesity is the failure of
weight loss programs to produce meaningful and sustained weight loss. It is unknown whether early life stress
worsens the maintenance of lost weight or whether exercise, which is the greatest predictor of weight loss
maintenance success, is effective in individuals that have experienced early life stress. Our overall hypothesis
is that early life stress impairs reward processing and homeostasis of body weight, which can be partially
mitigated by voluntary wheel running. We will test this overall hypothesis using neonatal maternal separation
(NMS) in mice, a preclinical model of early life stress. In Aim 1, we will determine if early life stress alters
reward sensitivity in response to high fat/high sucrose diet-induced obesity and calorie-restricted weight loss.
We expect that NMS mice will display hypercorticosteronemia, which will be negatively associated with
dopamine turnover and release in the NAc and VTA. We also anticipate that NMS mice will display altered
reward motivation when challenged with behavioral tests during diet-induced obesity and weight loss. In Aim 2,
we will test if early life stress potentiates weight regain and metabolic dysfunction and identify whether exercise
can counter these early life stress-induced impairments. We anticipate that NMS will cause an increased rate
of weight regain, inflammation, and metabolic dysfunction after being allowed to refeed ad libitum following
calorie-restricted weight loss. We expect that voluntary wheel running will attenuate weight regain and
metabolic dysfunction in naïve mice to a greater extent than in NMS mice. Given the increasing prevalence of
both obesity and early life stress, it is highly likely that this is an interaction impacting clinical weight loss
maintenance. It is vitally important to understand how early life stress alters reward motivation and weight loss
maintenance success to allow for the development of improved weight loss maintenance therapies and better
outcomes in obesity treatments.