The environmental obesogen hypothesis proposes that exposure to
endocrine disruptors during developmental 'window' contributes to adipogenesis and the development of
obesity.
MEHP [mono-(2-ethylhexyl)
phthalate], a metabolite of the widespread
plasticizer DEHP [di-(2-ethylhexyl)
phthalate], has been found in exposed organisms and identified as a selective PPARγ (
peroxisome-proliferator-activated receptor γ) modulator. However, implication of
MEHP on adipose tissue development has been poorly investigated. In the present study, we show the dose-dependent effects of
MEHP on adipocyte differentiation and GPDH (glycerol-3-phosphate dehydrogenase) activity in the murine 3T3-L1 cell model.
MEHP induced the expression of PPARγ as well as its target genes required for adipogenesis in vitro. Moreover,
MEHP perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to a low dose of
MEHP significantly increased b.w. (
body weight) and fat pad weight in male offspring at PND (postnatal day) 60. In addition, serum
cholesterol, TAG (
triacylglycerol) and
glucose levels were also significantly elevated. These results suggest that perinatal exposure to
MEHP may be expected to increase the incidence of
obesity in a sex-dependent manner and can act as a potential chemical stressor for
obesity and
obesity-related disorders.