Inhibition of human mesenchymal stem cell-derived adipogenesis by the environmental contaminant benzo(a)pyrene.
Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BP) are environmental contaminants exerting various toxic effects. PAHs have notably been found to inhibit adipogenesis in rodent species. To determine whether a similar process concerns human cells, we have analyzed the effects of BP towards differentiation of human cultured mesenchymal stem cells (MSC) into adipocytes, triggered by a pro-adipogenic culture medium. BP was found to markedly prevent formation of lipid vesicles, cellular lipid accumulation and up-regulation of adipogenic markers such as fatty acid binding protein-4 and glyceraldehyde-3-phosphate dehydrogenase, which represent major hallmarks of human MSC-derived adipocytes. The aryl hydrocarbon receptor (AhR), known to mediate most of the toxic effects of PAHs, was demonstrated to be present and functional in human MSC. 2,3,7,8-tetrachlorodibenzo-p-dioxin, an AhR agonist like BP, was found to inhibit lipid accumulation in human MSC cultured with adipogenic medium, in contrast to the PAH benzo(e)pyrene, known to not, or only poorly, interact with AhR. Moreover, BP inhibitory effect toward lipid accumulation in MSC exposed to adipogenic medium was fully counteracted by co-treatment with the AhR antagonist alpha-naphtoflavone. Taken together, these data indicate that environmental PAHs like BP can likely inhibit human adipogenesis in an AhR-dependent manner.
Podechard
Normand
N
EA-SeRAIC 4427/INSERM U620, Equipe Labellisée Ligue Nationale contre le Cancer, IFR140, Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes, Cedex, France.
Fardel
Olivier
O
Corolleur
Michel
M
Bernard
Marc
M
Lecureur
Valérie
V
D050156:Adipogenesis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D004785:Environmental Pollutants; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases