The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice.
Epidemiology studies indicate that exposure to endocrine disruptors during developmental "window" contributes to adipogenesis and the development of obesity. Implication of endocrine disruptor such as diethylstilbestrol (DES) on adipose tissue development has been poorly investigated. Here we evaluated the effects of DES on adipocyte differentiation in vitro and in vivo, and explored potential mechanism involved in its action. DES induced 3T3-L1 preadipocyte differentiation in a dose-dependent manner, and activated the expression of estrogen receptor (ER) and peroxisome proliferator-acivated receptor (PPAR) γ as well as its target genes required for adipogenesis in vitro. ER mediated the enhancement of DES-induced PPARγ activity. Moreover, DES perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to low dose of DES significantly increased body weight, liver weight and fat mass in female offspring at postnatal day (PND) 60. In addition, serum triglyceride and glucose levels were also significantly elevated. These results suggest that perinatal exposure to DES 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.
Reproductive and Genetic Center, National Research Institute for Family Planning, No. 12, Dahuisi Rd., Beijing 100081, PR China.
Chan-Juan
CJ
Hao
Xue-Jia
XJ
Cheng
Hong-Fei
HF
Xia
Xu
X
Ma
D041721:3T3-L1 Cells / Q000187:drug effects; D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced*; D060888:Real-Time Polymerase Chain Reaction
D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol; D005993:Glycerolphosphate Dehydrogenase