Chemicals found in house dust can activate an important human receptor linked to obesity, according to a US study.
The "master" receptor, peroxisome proliferator-activated nuclear receptor gamma (PPARgamma), regulates lipid metabolism, cell proliferation and cell death (CW 5 December 2013). There is growing evidence that PPARgamma activation may be a “key factor for obesity”, say the researchers, led by Heather Stapleton from Duke University.
In the past few years, a number of common environmental contaminants, including tributyltin and a metabolite of the phthalate DEHP, have been shown to activate the receptor. Dr Stapleton's team has recently found a wide range of chemicals, including organophosphates and polybrominated diphenyl ether (PBDE) metabolites, to bind to PPARgamma.
The team also discovered that chemicals in house dust samples bind to the receptor. “House dust is an important pathway for the uptake of environmental contaminants,” said co-author Mingliang Fang. Young children are the most exposed, ingesting about 50mg of dust per day, according to figures from the US EPA.
However, such binding does not necessarily activate the receptor. To investigate further, the team monitored PPARgamma activation, using a commercially available reporter gene assay. Their tests revealed that 28 of 30 common semi-volatile compounds (SVOCs) can do so. Meanwhile, 15 of 25 indoor dust samples, collected from homes, gyms and offices, showed “significant” PPARgamma activation.
Results varied for the different types of dust. A previous study had found higher concentrations of PBDEs in gymnasium dust, probably resulting from treated foam mats. However, the gym dust caused no obvious activation, perhaps suggesting that PBDEs are not the main culprits.
“This is the first time PPARgamma1 agonistic effects, from mixtures of chemicals present in house dust extracts, were found,” write the researchers in Environmental Science and Technology.
The study shows how seemingly small changes to structure can significantly affect receptor activation. For example, triphenyl phosphate (TPP) is more potent than its phosphite form. To bind, it would appear that chemicals need a long chain, says Mr Fang. Halogenation also seems to increase binding, he adds.
The researchers were interested to find that a tert-butyl phenyl diphenyl phosphate (BPDP) commercial flame retardant mixture - which contains TPP, BPDP isomers, dibutylphenyl and tributylphenyl phosphates - is more potent than TPP alone.
BPDP is "of interest", say the researchers, because it is not only used as a flame retardant but is also added to lubricants, hydraulic fluids and plastics.
Stapleton's team is currently studying how "environmentally realistic" chemical mixtures activate PPARgamma, with the possibility of the constituents having additive or synergistic effects.
“Our idea is to mimic real environmental exposure, with many chemicals, at low levels,” says Mr Fang. After running assays, the researchers use mathematical models to see whether the observed effects can be explained by a simple addition of chemicals in the mixture, or whether they may be acting synergistically.