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Effects of perfluorinated chemicals on adipocyte development
Citation:
Watkins, A., C. Wood, M. Lin, AND B. Abbott. Effects of perfluorinated chemicals on adipocyte development. Presented at Teratology Society Annual meeting, Tucson, AZ, June 22 - 26, 2013.
Impact/Purpose:
This abstract will be presented at the Teratology Society Annual meeting in Tucson, Arizona, June 22-26, 2013
Description:
Obesity is a growing concern in the US population. Current interest is high in the role played by environmental factors called obesogens that may contribute to obesity through developmental exposure. One class of potential obesogens is the family of perfluorinated chemicals used as surfactants in a variety of industrial applications. Given the importance of understanding the role these compounds play in lipid homeostasis we used pre-adipocyte 3T3-L1 mouse fibroblast cells (Zen-Bio, RTP NC) to study their effects on adipogenesis and lipid accumulation. These cells differentiate into adipocytes accumulating large lipid droplets. Cultures were treated with perfluorooctanoic acid (PFOA) (1-200uM), perfluorononanoic acid (PFNA) (5-lOOuM), perfluorooctane sulfonate (PFOS) (5O-300uM), and perfluorohexane sulfonate (PFHxS) (40- 250uM). Cell size number, and lipid content were assessed using morphomeiric analysis. All four compounds decreased cell size compared to control, and PFNA was most potent, in terms of lowest observed effect concentration (LOEC), whereas PFOA was least potent. Cell number increased for all perfluorinated chemicals tested, most potently for PFNA and least for PFOS. Interestingly, average lipid area per cell for all four chemicals decreased compared to control, but PFOS and PFHxS had increased total lipid area. Additionally, significant increases in total triglyceride were noted for all compounds compared to controls. PFOA and PFNA increased triglyceride most potently and PFOS was least effective. RNA was extracted for qPCR analysis of 13 genes. Three genes, acyl-coA-oxidase 1 (acox1), peroxisome proliferator-activated receptory coactivator 1 (PPARyc1), and glyceraldehyde-3-phosphate-dehydrogenase (GAPDI-1), were upregulated by all compounds. Both PPARa andy were upregulated by three of the chemicals. The strongest induction was of stearoyl-coA-desaturase (scd-1) by PFHxS, producing nearly ten-fold upregulation. PFHxS was also the most active compound affecting 12 of the 13 genes studied. In summary, these results demonstrate that the perfluorinated chemicals stimulate pre-adipocyte cell proliferation and differentiation, and increase lipid accumulation in mature adipocytes. These effects appear to involve activation of PPARa and y and other genes associated with lipid regulation. (This abstract does not necessarily express US EPA policy.)