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• W2000345603 abstract "Vol. 122, No. 11 News | Science SelectionsOpen AccessMore Fat, Less Bone? Flame Retardant May Deliver a One–Two Punchis accompanied byLigand Binding and Activation of PPARγ by Firemaster® 550: Effects on Adipogenesis and Osteogenesis in Vitro Wendee Nicole Wendee Nicole Search for more papers by this author Published:1 November 2014https://doi.org/10.1289/ehp.122-A312View Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Firemaster® 550 (FM550) was introduced in 2003 as an alternative to the toxic, persistent flame retardant pentabromodiphenyl ether, for use in mattresses, couches, and other items containing polyurethane foam.1 FM550 contains a mixture of brominated phthalates and organophosphates. In 2013 a groundbreaking study found that pre- and postnatal exposure to FM550 was associated with increased anxiety, obesity, and early-onset puberty in rats, raising concern over the continued use of these chemicals.2 In this issue of EHP, a team of investigators report further evidence that components of FM550 may act as environmental obesogens, stimulating adipogenesis (fat formation) at the expense of bone health.3House dust can be a major source of exposure to flame retardants.Finger: © Gunnar Pippel/Shutterstock; TPP molecule: Pillai et al. (2014)3Using computer modeling and receptor binding and activity assays, the authors of the current study found that the phosphate components of FM550 bound to and activated peroxisome proliferator–activated receptor γ, the master regulator of adipogenesis. The brominated components of FM550 did not. Using multipotent mesenchymal stromal cells from rats, they also showed that FM550 and its constituent triphenyl phosphate (TPP) stimulated formation of fat cells.3When stem cells differentiate into fat cells, they do so at the expense of bone and cartilage formation.4 In this study, both FM550 and TPP suppressed osteogenesis in bone marrow cultures, with FM550 suppressing activity more than TPP alone.3 The authors hypothesize that environmental obesogens could be contributing to the growing prevalence of osteoporosis worldwide.5House dust contains high levels of organophosphate flame retardants, and their metabolites are ubiquitous in human urine.6 The authors estimated that young children could ingest 120 μg/day TPP from indoor exposure to dust alone.3“The effects shown in this paper occur at significantly higher exposures; thus, at present exposure levels there seems to be a margin of safety,” says Jerry Heindel, a health scientist administrator at the National Institute of Environmental Health Sciences, which supported the study in part. “However, if exposure increases due to increased use of FM550, the margin of safety could be eroded.”According to Barbara Corkey, director of the Obesity Research Center at Boston University School of Medicine, the new study is important to the field “because FM550 is one of thousands of chemicals that have appeared in our environment since the obesity epidemic began. The important question this study raises is how many of the other thousands of compounds that have not been tested [may] also have a small effect on obesity.” Corkey was not involved in the research.“This is the first study to provide evidence that an organophosphate-based flame retardant could contribute to bone loss,” says coauthor Jennifer Schlezinger, an associate professor of environmental health at Boston University School of Public Health. Although the idea that environmental chemicals could be contributing to the obesity epidemic is gaining ground,4 “few people think about what the consequences of environmental nuclear receptor ligands may be in the bone,” Schlezinger says.Other research has found that the anti-diabetes drug rosiglitazone both increases the risk of bone fracture and acts as an obesogen,7 and tributyltin has been shown to induce adipogenesis and suppress osteogenesis.8 Arsenic and lead also may inhibit bone formation.9,10 “Each time I find that a chemical can suppress bone formation I become more intrigued and concerned with the idea that common environment contaminants are contributing to the onset or exacerbation of osteoporosis,” Schlezinger adds.“This is a good study because it is comprehensive, asking the same question multiple times with different assays,” says Heindel. “These data match the physiology, as TPP … is structurally similar to tributyltin, which causes these same effects but at lower doses.”The next steps will involve an expanded, improved risk assessment to the human population, Heindel says. “It is highly likely that similar effects will be seen in humans, as all these same pathways exist,” he says. “Indeed, tributyltin has been shown to affect human mesenchymal stem cells in the same manner as rodent stem cells used here.”11References1 Stapleton HMet al.Alternate and new brominated flame retardants detected in U.S. house dust.Environ Sci Technol 42(18):6910-69162008.; doi:10.1021/es801070p18853808. Crossref, Medline, Google Scholar2 Patisaul HBet al.Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster 550® in rats: an exploratory assessment.J Biochem Mol Toxicol 27(2):124-1362013.; doi:10.1002/jbt.2143923139171. Crossref, Medline, Google Scholar3 Pillai HKet al.Ligand binding and activation of PPARγ by Firemaster® 550: effects on adipogenesis and osteogenesis in vitro.Environ Health Perspect 122(11):1225-12322014.; doi:10.1289/ehp.140811125062436. Link, Google Scholar4 Janesick A, Blumberg BEndocrine disrupting chemicals and the developmental programming of adipogenesis and obesity.Birth Defects Res C Embryo Today 93(1):34-502011.; doi:10.1002/bdrc.2019721425440. Crossref, Medline, Google Scholar5 Sànchez-Riera Let al.The global burden attributable to low bone mineral density.Ann Rheum Dis 73(9):1635-16452014.; doi:10.1136/annrheumdis-2013-20432024692584. Crossref, Medline, Google Scholar6 Meeker JDet al.Urinary metabolites of organophosphate flame retardants: temporal variability and correlations with house dust concentrations.Environ Health Perspect 121(5):580-5852013.; doi:10.1289/ehp.120590723461877. Link, Google Scholar7 Kahn SEet al.Rosiglitazone-associated fractures in type 2 diabetes: an analysis from A Diabetes Outcome Progression Trial (ADOPT).Diabetes Care 31(5):845-8512008.; doi:10.2337/dc07-227018223031. Crossref, Medline, Google Scholar8 Kirchner Set al.Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes.Mol Endocrinol 24(3):526-5392010.; doi:10.1210/me.2009-026120160124. Crossref, Medline, Google Scholar9 Beier EEet al.Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling.Environ Health Perspect 121(1):97-1042013.; doi:10.1289/ehp.120537423086611. Link, Google Scholar10 Wu CTet al.Effects of arsenic on osteoblast differentiation in vitro and on bone mineral density and microstructure in rats.Environ Health Perspect 122(6):559-5652014.; doi:10.1289/ehp.130783224531206. Link, Google Scholar11 Chamorro-García Ret al.Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal exposure to the obesogen tributyltin in mice.Environ Health Perspect 121(3):359-3662013.; doi:10.1289/ehp.120570123322813. Link, Google ScholarFiguresReferencesRelatedDetailsRelated articlesLigand Binding and Activation of PPARγ by Firemaster® 550: Effects on Adipogenesis and Osteogenesis in VitroJul 25, 2014, 12:00:00 AMEnvironmental Health Perspectives Vol. 122, No. 11 November 2014Metrics Downloaded 167 times About Article Metrics Publication History Originally published1 November 2014Published in print1 November 2014 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days." @default.
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