Dissertation
The Epigenetic Transgenerational Inheritance of Obesity and Adult Onset Diseases
Doctor of Philosophy (PhD), Washington State University
01/2019
Handle:
https://hdl.handle.net/2376/117120
Abstract
The incidence of obesity has increased dramatically over the past two decades with a prevalence of 39.6% of the population in the United States in 2016. Obesity dramatically increases the risk for cardiovascular disease, type II diabetes, non-alcoholic fatty liver disease, cancer, stroke, and kidney disease. While genetic and lifestyle causes have been identified in obesity, ancestral prenatal exposure to environmental toxicants has been shown to increase the susceptibility to obesity. During a previous investigation of the epigenetic transgenerational inheritance of disease in rats ancestrally exposed to the pesticide dichlorodiphenyltrichloroethane (DDT), 50% of the rat population developed obesity. In a similar investigation of the transgenerational effects of prenatal atrazine exposure, 56% of female rats and 30% of male rats developed a lean phenotype. The goal of these studies is to test the hypothesis that ancestral exposure to environmental toxicants induces the epigenetic transgenerational inheritance of germline epimutations that promote alterations in the epigenome of differentiated adipocytes which increase the susceptibility to lean and obese phenotypes. We used a transgenerational model of ancestral prenatal exposure to DDT and atrazine in order to identify novel epigenetic aspects for lean and obese phenotypes. We investigated and further elucidated the obese and lean phenotypes seen in both the control colony and rats ancestrally exposed to atrazine or DDT; investigated germline epimutations associated with the increased susceptibility to obese and lean phenotypes in the transgenerational models; 3) determined the adipocyte epigenetic alterations in the obese and lean phenotypes in the transgenerational models. The completed research will help illuminate the epigenetic transgenerational inheritance of lean and obese phenotypes as well as determine the impacts of ancestral exposures on the susceptibility of disease. This is a novel mechanism to consider in the etiology of obesity and will provide insight into future human studies as well as potential disease therapies.
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Details
- Title
- The Epigenetic Transgenerational Inheritance of Obesity and Adult Onset Diseases
- Creators
- Stephanie E King
- Contributors
- Michael K Skinner (Advisor)Patrick A Carter (Committee Member)Glen E Duncan (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- School of Biological Sciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 174
- Identifiers
- 99900581707001842
- Language
- English
- Resource Type
- Dissertation