Laboratory in vitro data have clearly and consistently demonstrated the potential mechanisms associated with the interference of exposure to POPs with obesity, including: (i) the effects on adipogenesis regulators (PPARγ, C/EBPα); (ii) the endocrine-disrupting effects and binding to nuclear receptors (ER, GR); (iii) the epigenetic effects; (iv) proinflammatory activity; and (v) the induction of insulin resistance. Here, PPARG is linked to obesity due to melanocortin 4 receptor deficiency.