Based on our recent findings that showed ID3 dependent endothelial cell activation by exposure to estrogenic PCB congener 153 [10, 11], we will also discuss how low-dose EDC exposure from the environment may potentiate complex chronic disease in populations with metabolic disorders (obesity, metabolic syndrome, and glucose intolerance) via ID3. Here, ID3 is linked to obesity due to melanocortin 4 receptor deficiency.