Perinatal exposure to diethyl-hexyl-phthalate induces obesity in mice.

The environmental obesogen hypothesis proposes that exposure to endocrine disruptors during developmental "window" contributes to adipogenesis and the development of obesity. Implication of environmental endocrine disruptor such as diethyl-hexyl-phthalate (DEHP) on adipose tissue development has been poorly investigated. Here, we evaluated the effects of DEHP on adipocyte differentiation in vitro and in vivo, and explored potential mechanism involved in its action. DEHP had no effect on adipocyte differentiation in the murine 3T3-L1 cell model, whereas DEHP induced the expression of transcriptional factors peroxisome proliferator-activated receptor (PPAR) gamma, CCAAT/enhancer-binding protein (C/EBP) alpha and sterol regulatory element binding factor 1 (Srebf1) as well as downstream target genes required for adipogenesis in vivo. Furthermore, perinatal exposure to DEHP had an impact on filial adipogenesis. Body weight, adipose tissue deposition, serum lipids and glucose levels were significantly elevated in offspring at postnatal day (PND) 60. Therefore, these results suggested that perinatal exposure to DEHP might be expected to increase the incidence of obesity in offspring and could act as a potential chemical stressor for obesity and obesity-related disorders.