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Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect
Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs) in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796469/ https://www.ncbi.nlm.nih.gov/pubmed/24155963 http://dx.doi.org/10.1371/journal.pone.0077481 |
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author | Pereira-Fernandes, Anna Demaegdt, Heidi Vandermeiren, Karine Hectors, Tine L. M. Jorens, Philippe G. Blust, Ronny Vanparys, Caroline |
author_facet | Pereira-Fernandes, Anna Demaegdt, Heidi Vandermeiren, Karine Hectors, Tine L. M. Jorens, Philippe G. Blust, Ronny Vanparys, Caroline |
author_sort | Pereira-Fernandes, Anna |
collection | PubMed |
description | Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs) in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD) method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds), were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ) dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA). PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound. |
format | Online Article Text |
id | pubmed-3796469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37964692013-10-23 Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect Pereira-Fernandes, Anna Demaegdt, Heidi Vandermeiren, Karine Hectors, Tine L. M. Jorens, Philippe G. Blust, Ronny Vanparys, Caroline PLoS One Research Article Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs) in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD) method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds), were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ) dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA). PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound. Public Library of Science 2013-10-14 /pmc/articles/PMC3796469/ /pubmed/24155963 http://dx.doi.org/10.1371/journal.pone.0077481 Text en © 2013 Pereira-Fernandes et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Pereira-Fernandes, Anna Demaegdt, Heidi Vandermeiren, Karine Hectors, Tine L. M. Jorens, Philippe G. Blust, Ronny Vanparys, Caroline Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect |
title | Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect |
title_full | Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect |
title_fullStr | Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect |
title_full_unstemmed | Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect |
title_short | Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect |
title_sort | evaluation of a screening system for obesogenic compounds: screening of endocrine disrupting compounds and evaluation of the ppar dependency of the effect |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796469/ https://www.ncbi.nlm.nih.gov/pubmed/24155963 http://dx.doi.org/10.1371/journal.pone.0077481 |
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