Role of environmental toxicants in obesity-related cardiovascular disease

Lipophilic pollutants, particularly persistent organic pollutants (POPs), bioaccumulate in adipose tissue. We hypothesize that sequestration of pollutants in adipose tissues is detrimental to cardiometabolic health and disproportionately impacts obese individuals. Our funded NIH parent grant examines mechanisms of vascular dysfunction in obesity. Adipose tissue dysfunction, inflammation, and insulin resistance are essential hallmarks linking obesity to the pathogenesis of cardiovascular disease. We hypothesize that pollutants that accumulate in fat depots promote adipose tissue dysfunction, in part, by activating inflammatory and pro-atherogenic signaling pathways implicated in the pathogenesis of cardiovascular disease. We propose to use both targeted and untargeted analyses of pollutants in adipose tissues and blood from lean individuals and obese subjects at the time of bariatric surgery, with repeat measures 6-months after marked (20-30%) weight loss. We will relate POP and novel pollutant measures to clinical and vascular parameters of cardiometabolic risk and study the impact of weight loss.