Effect-Directed
Analysis of Human Peroxisome Proliferator-Activated
Nuclear Receptors (PPARγ1) Ligands in Indoor Dust
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Abstract
Agonism
of human peroxisome proliferator-activated nuclear receptor
gamma (PPARγ1) was recently observed in 15 of 25 samples of
indoor dust extracts at environmentally relevant exposure levels.
In this study, an effect-directed analysis approach was used to identify
the primary contributors of PPARγ1 activity in the dust extracts.
Three dust extracts showing significant PPARγ1 activity were
fractionated with normal phase high-performance liquid chromatography
(NP-HPLC) and each fraction was tested for PPARγ1 activity.
Three dust extracts showed a similar PPARγ1 activity distribution
in the NP-HPLC fractions. In most active fractions, fatty acids (FAs),
including oleic acid, stearic acid, palmitic acid and myristic acid,
were the primary chemicals identified using gas-chromatography mass
spectrometry (GC-MS). Chemical measurements of the FAs in house dust
extracts revealed a positive and significant correlation with the
observed PPARγ1 activity. To test the role of FAs in the activity,
a mixture of four FAs was prepared in the ratios measured in the dust
samples and tested for activity. The activity of this mixture was
30–50% of the activity observed in the dust extracts, suggesting
they were contributing to the observed activity, but also suggesting
additional unknown compounds are likely still present in the dust
extracts. To tentatively identify sources of FAs in the dust samples,
FAs were quantified in human/animal hair, dead skin cells, and cooking
oil. FAs were abundant in all samples and our data indicate that all
of these may be sources to indoor dust