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Effect-Directed Analysis of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPAR?1) Ligands in Indoor Dust.

ABSTRACT: Agonism of human peroxisome proliferator-activated nuclear receptor gamma (PPAR?1) 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 PPAR?1 activity in the dust extracts. Three dust extracts showing significant PPAR?1 activity were fractionated with normal phase high-performance liquid chromatography (NP-HPLC) and each fraction was tested for PPAR?1 activity. Three dust extracts showed a similar PPAR?1 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 PPAR?1 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.

SUBMITTER: Fang M

PROVIDER: S-EPMC4786017 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Effect-Directed Analysis of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPARγ1) Ligands in Indoor Dust.

Fang Mingliang M Webster Thomas F TF Stapleton Heather M HM

Environmental science & technology 20150730 16

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 test ...[more]

PMID: 26172369

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Project description:Cannabinoids act at two classical cannabinoid receptors (CB1 and CB2), a 7TM orphan receptor and the transmitter-gated channel transient receptor potential vanilloid type-1 receptor. Recent evidence also points to cannabinoids acting at members of the nuclear receptor family, peroxisome proliferator-activated receptors (PPARs, with three subtypes alpha, beta (delta) and gamma), which regulate cell differentiation and lipid metabolism. Much evidence now suggests that endocannabinoids are natural activators of PPAR alpha. Oleoylethanolamide regulates feeding and body weight, stimulates fat utilization and has neuroprotective effects mediated through activation of PPAR alpha. Similarly, palmitoylethanolamide regulates feeding and lipid metabolism and has anti-inflammatory properties mediated by PPAR alpha. Other endocannabinoids that activate PPAR alpha include anandamide, virodhamine and noladin. Some (but not all) endocannabinoids also activate PPAR gamma; anandamide and 2-arachidonoylglycerol have anti-inflammatory properties mediated by PPAR gamma. Similarly, ajulemic acid, a structural analogue of a metabolite of Delta(9)-tetrahydrocannabinol (THC), causes anti-inflammatory effects in vivo through PPAR gamma. THC also activates PPAR gamma, leading to a time-dependent vasorelaxation in isolated arteries. Other cannabinoids which activate PPAR gamma include N-arachidonoyl-dopamine, HU210, WIN55212-2 and CP55940. In contrast, little research has been carried out on the effects of cannabinoids at PPAR delta. In this newly emerging area, a number of research questions remain unanswered; for example, why do cannabinoids activate some isoforms and not others? How much of the chronic effects of cannabinoids are through activation of nuclear receptors? And importantly, do cannabinoids confer the same neuro- and cardioprotective benefits as other PPAR alpha and PPAR gamma agonists? This review will summarize the published literature implicating cannabinoid-mediated PPAR effects and discuss the implications thereof.

Dataset Information

Effect-Directed Analysis of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPAR?1) Ligands in Indoor Dust.

Publications

Effect-Directed Analysis of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPARγ1) Ligands in Indoor Dust.

Similar Datasets

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