Environmental Endocrine Disruptors Promote Adipogenesis in the 3T3‐L1 Cell Line through Glucocorticoid Receptor Activation

Environmental Endocrine Disruptors Promote Adipogenesis in the 3T3‐L1 Cell Line through... The burgeoning obesity and diabetes epidemics threaten health worldwide, yet the molecular mechanisms underlying these phenomena are incompletely understood. Recently, attention has focused on the potential contributions of environmental pollutants that act as endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases. Because glucocorticoid signaling is central to adipocyte differentiation, the ability of EDCs to stimulate the glucocorticoid receptor (GR) and drive adipogenesis was assessed in the 3T3‐L1 cell line. Various EDCs were screened for glucocorticoid‐like activity using a luciferase reporter construct, and four (bisphenol A (BPA), dicyclohexyl phthalate (DCHP), endrin, and tolylfluanid (TF)) were shown to significantly stimulate GR without significant activation of the peroxisome proliferator‐activated receptor‐γ. 3T3‐L1 preadipocytes were then treated with EDCs and a weak differentiation cocktail containing dehydrocorticosterone (DHC) in place of the synthetic dexamethasone. The capacity of these compounds to promote adipogenesis was assessed by quantitative oil red O staining and immunoblotting for adipocyte‐specific proteins. The four EDCs increased lipid accumulation in the differentiating adipocytes and also upregulated the expression of adipocytic proteins. Interestingly, proadipogenic effects were observed at picomolar concentrations for several of the EDCs. Because there was no detectable adipogenesis when the preadipocytes were treated with compounds alone, the EDCs are likely promoting adipocyte differentiation by synergizing with agents present in the differentiation cocktail. Thus, EDCs are able to promote adipogenesis through the activation of the GR, further implicating these compounds in the rising rates of obesity and diabetes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Obesity Wiley

Environmental Endocrine Disruptors Promote Adipogenesis in the 3T3‐L1 Cell Line through Glucocorticoid Receptor Activation

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Publisher
Wiley
Copyright
2010 North American Association for the Study of Obesity (NAASO)
ISSN
1930-7381
eISSN
1930-739X
DOI
10.1038/oby.2009.419
Publisher site
See Article on Publisher Site

Abstract

The burgeoning obesity and diabetes epidemics threaten health worldwide, yet the molecular mechanisms underlying these phenomena are incompletely understood. Recently, attention has focused on the potential contributions of environmental pollutants that act as endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases. Because glucocorticoid signaling is central to adipocyte differentiation, the ability of EDCs to stimulate the glucocorticoid receptor (GR) and drive adipogenesis was assessed in the 3T3‐L1 cell line. Various EDCs were screened for glucocorticoid‐like activity using a luciferase reporter construct, and four (bisphenol A (BPA), dicyclohexyl phthalate (DCHP), endrin, and tolylfluanid (TF)) were shown to significantly stimulate GR without significant activation of the peroxisome proliferator‐activated receptor‐γ. 3T3‐L1 preadipocytes were then treated with EDCs and a weak differentiation cocktail containing dehydrocorticosterone (DHC) in place of the synthetic dexamethasone. The capacity of these compounds to promote adipogenesis was assessed by quantitative oil red O staining and immunoblotting for adipocyte‐specific proteins. The four EDCs increased lipid accumulation in the differentiating adipocytes and also upregulated the expression of adipocytic proteins. Interestingly, proadipogenic effects were observed at picomolar concentrations for several of the EDCs. Because there was no detectable adipogenesis when the preadipocytes were treated with compounds alone, the EDCs are likely promoting adipocyte differentiation by synergizing with agents present in the differentiation cocktail. Thus, EDCs are able to promote adipogenesis through the activation of the GR, further implicating these compounds in the rising rates of obesity and diabetes.

Journal

ObesityWiley

Published: Jul 1, 2010

References

  • Understanding adipocyte differentiation
    Gregoire, Gregoire; Smas, Smas; Sul, Sul
  • Xenobiotics and the glucocorticoid receptor: additive antagonistic effects on tyrosine aminotransferase activity in rat hepatoma cells
    Johansson, Johansson; Johansson, Johansson; Lund, Lund
  • Disruption of glucocorticoid action by environmental chemicals: potential mechanisms and relevance
    Odermatt, Odermatt; Gumy, Gumy; Atanasov, Atanasov; Dzyakanchuk, Dzyakanchuk
  • Hormonal regulation of adiponectin gene expression in 3T3‐L1 adipocytes
    Fasshauer, Fasshauer; Klein, Klein; Neumann, Neumann; Eszlinger, Eszlinger; Paschke, Paschke
  • The modulation of STAT5A/GR complexes during fat cell differentiation and in mature adipocytes
    Baugh, Baugh; Floyd, Floyd; Stephens, Stephens
  • Exposure of women to organochlorine pesticides in Southern Spain
    Botella, Botella; Crespo, Crespo; Rivas, Rivas
  • Thiazolidinediones, insulin resistance and obesity: Finding a balance
    Wilding, Wilding

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