UC Berkeley

Arsenic, a naturally occurring metalloid, has been linked to a wide variety of metabolic disorders and diseases, including type II diabetes and non-alcoholic fatty liver disease. However, the exact mechanism of action of which arsenic leads to these maladies is not well understood. Research has elucidated the importance of other external factors, such as stress and diet, that may be increasing the development and severity of arsenic’s negative impacts. This dissertation aims to explore the combinatorial effects of arsenic and the lifestyle factors: diet and stress. Chapter I is an overview of how ubiquitous arsenic is in the world and how one unique population located in Antofagasta, Chile, has become a natural experiment in epidemiology given their clear start and stop exposure time frame and subsequent arsenic-linked disease incidence. This population in addition to others around the world, most notably those in Mexico, Bangladesh, and India, are the inspiration for the studies included in this dissertation. Chapter II evaluates a high fructose diet in combination with both low and high dose arsenic in an in vivo model. Both fructose and arsenic are metabolized in the liver and when in surplus can lead to dysregulation of triglyceride processing and storage. This study contributes to existing research on dietary influence on the adverse effects of arsenic exposure, which until now has been focused solely on high fat diets. Chapter III seeks to evaluate if arsenic antagonizes the glucocorticoid receptor by using an in vivo model exposed to both arsenic and a synthetic glucocorticoid. . Furthermore, there is a large person-to-person variation in susceptibility, but the majority of the reasons are unknown, making these studies crucial to determine where that susceptibility may lie.