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Investigating the effects of early life stress and high-fat/high-sucrose diet on hypothalamic gene expression, body weight regulation, and metabolic outcomes in mice
Frick, Jenna
Frick, Jenna
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Abstract
Exposure to early life stress has long been associated with increased risk of comorbid disorders in adulthood. Importantly, this stress exposure increases risk of obesity, metabolic disorder, eating disorders, and chronic pain syndromes. In addition to stress exposure, other lifestyle factors such as consumption of a Western style diet also contribute to greater risk of obesity development. However, the combined effects of early life stress and Western style diet on body weight and metabolic health throughout the lifespan are not well established. The overall goal of this dissertation is to examine the combined effects of early life stress and Western style diet on body weight and metabolic health, and to investigate potential behavioral and physiological changes underlying early life stress-induced weight gain. To do this, I used a mouse model of early life stress, neonatal maternal separation (NMS), which results in increased body weight, adiposity, mechanical hypersensitivity, and dysregulation of the hypothalamic-pituitary-adrenal axis. This dissertation investigates the combined effects of NMS and high-fat/high-sucrose (HFS) diet in male and female NMS and non-stressed (naïve) mice; to examine how stress influences susceptibility to diet-induced weight gain and to assess changes in energy intake, energy expenditure, feeding behavior, and hypothalamic gene expression which may underlie stress and diet-induced weight gain. These outcomes were examined in early life, peripuberty, and adulthood to determine age of onset.This work provides insight into the substantial effects that environmental factors such as early life stress and diet have on behavioral and health outcomes. Additionally, this research highlights the complex interactions of stress and diet and reveals sex differences in stress and diet-induced changes in body weight, adiposity, feeding behavior, and hypothalamic gene expression. These studies are novel as they examine the combined effects of multiple environmental factors and because they evaluate outcomes at multiple timepoints to identify age of condition onset.
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2023-05-31
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University of Kansas
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This item contains archived web content.
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985423_1.pdf
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Keywords
Neurosciences, Appetite, Early life stress, High-fat/high-sucrose diet, Hypothalamus, Neuroscience, Obesity