Screening assay for environmental obesogens acting via PPARs

Details

• Personal Author:
  Johnson VJ ; Luster M ; Wang W ; Yao J
• Description:
  The U.S. population is exposed to a number of environmental chemicals termed endocrine disruptors that may be associated with the increasing incidence of metabolic disorders and obesity, particularly in children. A number of these chemicals are believed to act as peroxisome proliferator activated receptor (PPAR) agonists and affect homeostatic pathways associated with glucose metabolism, lipid metabolism and inflammatory responses. The health consequences of aberrant PPAR activation are potentially significant and include increased risk for obesity, type-2 diabetes, cardiovascular disease and chronic inflammatory diseases. Studies were conducted to establish a high throughput in vitro cell culture screening assay to identify gene expression changes in key biological pathways that occur from putative environmental PPAR agonists using a low-density focused array card followed by RNA silencing studies of the PPARa and PPARg genes using selected human cell lines including THP1 cells, a human monocyte cell line. In our hands we found this approach to lack high sensitivity due to the multiple cell manipulations required. However, some of the more potent responses associated with treatment with positive controls (fibrate and glitazone) and test chemicals (such as tributyltin chloride and perfluorooctanoate) indicated that PPARa, PPARg or both were associated with the regulation of genes associated with several pathways including cholesterol homeostasis and acute phase proteins. Our results should be helpful particularly in epidemiological studies of children exposed to environmental obesogens as it provides potentially biologically relevant markers that can be examined. [Description provided by NIOSH]
• Subjects:
  Biological Assay Biomarkers Body Weight Cells, Cultured Endocrine System Environmental Exposure Epidemiology Genetics Occupational Health Safety Toxicology

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• Keywords:
  Author Keywords: Screaning Methods Bioassays Biological-systems Body-weight Cell-culture-techniques Cell-cultures Children Endocrine-function Environmental-exposure Genes Humans In-vitro-study Medical-screening Obesogen Peroxisome Proliferator Proteins Recombinant-DNA

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; North Carolina ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20046046
• Citation:
  Toxicologist 2015 Mar; 144(1)(Abstract Suppl):156
• CAS Registry Number:
  Tributyltin chloride (CAS RN 1461-22-9)
• Federal Fiscal Year:
  2015
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Supplement:
  Abstract Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:69067a14763b31252f861bc624c009c7f43c6de3c8e619f68bf2198b5423b0fc24e846445de413fa08d3070894f6f3f1e50680a6f3f962afc57dfacaca6e8b13
• Download URL:
  https://stacks.cdc.gov/view/cdc/201230/cdc_201230_DS1.pdf
• File Type:
  [PDF - 3.17 MB ]