title: The endocrine disruptor mono-(2-ethylhexyl) phthalate promotes adipocyte differentiation and induces obesity in mice.
abstract: 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.
authors.affiliation: Reproductive and Genetic Center, National Research Institute for Family Planning, Beijing, People’s Republic of China. genetic@263.net.cn
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Hao
authors.forename: Xuejia
authors.initials: X
authors.lastname: Cheng
authors.forename: Hongfei
authors.initials: H
authors.lastname: Xia
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004051:Diethylhexyl Phthalate / Q000009:adverse effects / Q000031:analogs & derivatives*; D052244:Endocrine Disruptors / Q000009:adverse effects*; D005260:Female; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D052244:Endocrine Disruptors; D008055:Lipids; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate