ABSTRACT
BACKGROUND/AIM: 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 4Nonylphenol (4-NP) on adipose tissue development has been poorly investigated. METHODS: 3T3-L1 preadipocytes were incubated with different doses of 4-NP. Six-week-old C57BL/6J male mice received an intraperitoneal injection of vehicle, troglitazone or 4-NP (0.5 mg/kg). Gene expression of adipogenic regulators was analyzed. Pregnant mice were dosed by gavage with vehicle or 4-NP (0.05, 0.25 or 0.5 mg/kg) from day 12 of gestation until day 7 of lactation. The body weight, liver weight, fat mass, and serum lipids and glucose levels were measured in offspring at postnatal day 60. RESULTS: Low concentration of 4-NP induced adipocyte differentiation, glycerol-3-phosphate dehydrogenase activity, and expression of peroxisome proliferator-acivated receptor γ as well as its target genes required for adipogenesis. 4-NP perturbed key regulators of adipogenesis and lipogenic pathway in vivo. Perinatal exposure to 4-NP increased body weight, fat mass, and serum total cholesterol and glucose levels in offspring. CONCLUSIONS: 4-NP may be expected to increase the incidence of obesity and can act as a potential chemical stressor for obesity and obesity-related disorders.
Subject(s)
Cell Differentiation/drug effects , Endocrine Disruptors/toxicity , Obesity/chemically induced , Phenols/toxicity , 3T3-L1 Cells , Adipogenesis/drug effects , Animals , Animals, Newborn , Blood Glucose/analysis , Body Weight/drug effects , Cholesterol/blood , Female , Glycerolphosphate Dehydrogenase/metabolism , Incidence , Lipids/blood , Liver/drug effects , Liver/physiology , Male , Mice , Mice, Inbred C57BL , Obesity/metabolism , PPAR gamma/metabolism , Pregnancy , Prenatal Exposure Delayed EffectsABSTRACT
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.
