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http://hdl.handle.net/11375/24594
Title: | The environmental toxin, chlorpyrifos disrupts mitochondrial function in brown adipose tissue and promotes the development of obesity and metabolic dysfunction in mice |
Authors: | Zhang, Shuman |
Advisor: | Steinberg, Gregory |
Department: | Medical Sciences |
Publication Date: | Jun-2019 |
Abstract: | Chlorpyrifos, one of the most utilized organophosphate pesticides worldwide, is commonly found on many fruits and vegetables, and has been associated with the development of obesity. Brown adipose tissue (BAT) has an abundance of multilocular lipid droplets and mitochondria that express uncoupling protein-1, a protein which generates a futile cycle that contributes to resting energy expenditure in rodents and humans. Reductions in BAT activity are associated with the development of obesity and related metabolic comorbidities including insulin resistance and non-alcoholic fatty liver disease (NAFLD). In this thesis, chlorpyrifos, at a dose which mimics non-occupational exposure, was fed to mice in combination with a control low fat or a high-fat diet and mice were maintained at either room temperature or at thermoneutrality. On a control diet chlorpyrifos had minimal effects on obesity and glucose homeostasis but when combined with a high-fat diet it was found to promote obesity, non-alcoholic liver disease and insulin resistance; effect was more prominent at thermoneutrality. This effect of chlorpyrifos in high-fat diet fed mice was associated with reduced expression of uncoupling protein-1, and disruption of mitochondrial homeostasis within brown adipose tissue, an effect associated with reductions in AMPK and markers of mitophagy. These data suggest that chlorpyrifos may promote obesity and metabolic dysfunction by suppressing brown adipose tissue mitochondrial function. |
URI: | http://hdl.handle.net/11375/24594 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Zhang_Shuman_201906_MSc.pdf | 1.25 MB | Adobe PDF | View/Open |
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