Obesity is at epidemic proportions in the US, with 64.5% of the adult population considered overweight. Kentucky, a state with numerous Superfund sites on the National Priority List, has the 4th highest prevalence of obesity in the nation. Recent studies suggest that obesity is a state of low grade inflammation, thought to link obesity to several different diseases. Importantly, cardiovascular diseases such as atherosclerosis, are the most common cause of death in the obese population. Moreover, recent studies demonstrate that obesity can promote formation of abdominal aortic aneurysms (AAAs). Interestingly, both of these vascular pathologies exhibit pronounced inflammation.

Polychlorinated biphenyls (PCBs), highly lipophilic superfund chemicals that concentrate in adipose tissue, have also been linked to inflammation. When exposed to PCBs, obese individuals have higher adipose accumulation than lean subjects, with PCB serum levels linked to the metabolic diseases associated with obesity. During the previous period of support, we demonstrated that certain PCBs can promote formation of new fat cells, and also increase expression of proinflammatory substances produced by adipocytes. Moreover, we demonstrated that these effects of PCBs were associated with an increase in body weight. Importantly, PCB exposure increased atherosclerosis and AAAs, diseases promoted by obesity.

In Specific Aim 1, we will examine whether specific PCBs promote oxidative stress in adipocytes as a mechanism promoting inflammation. Moreover, we will define whether these effects of PCBs are influenced by specific types of fatty acids. Specifically, we hypothesize that saturated fatty acids, linked to cardiovascular disease, will magnify effects of PCBs to promote inflammation in adipocytes.

In Specific Aim 2, we will define the role of the arylhydrocarbon receptor (AhR) within fat cells on the ability of PCBs to promote obesity, and obesity-induced AAA formation. 

In Specific Aim 3, we will define whether specific types of dietary fatty acids either ameliorate (healthy omega-3 fatty acids) or potentiate (saturated and/or omega-6 fatty acids) PCB-induced obesity and AAA formation.