KMID : 1034820180140040369
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Molecular & Cellular Toxicology 2018 Volume.14 No. 4 p.369 ~ p.379
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Trends in gene expression changes during adipogenesis in human adipose derived mesenchymal stem cells under dichlorodiphenyldichloroethylene exposure
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Pesta Martin
Cedikova Miroslava Dvorak Pavel Dvorakova Jana Kulda Vlastimil Srbecka Kristyna Muller Ludek Bouchalova Vendula Kralickova Milena Babuska Vaclav Kuncova Jitka Mullerova Dana
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Abstract
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Backgrounds: Exposure to lipophilic environmental pollutants has been explored as a risk factor of development of diabetes mellitus in obese. Adipose tissue is a reservoir of bioaccumulative lipophilic contaminants including p,p?-dichlorodiphenyldichloroethylene (DDE). Our aim was to analyze the effect of DDE (in concentrations 0.1 ¥ìM, 1 ¥ìM, and 10 ¥ìM) on adipocyte differentiation and insulin signalling pathway on in vitro adipogenic model of human adipose derived mesenchymal stem cells (hADMSC).
Methods: The effect of DDE was monitored by analysis of expression (RT qPCR, Western blotting) of genes involved in adipocyte differentiation and insulin signalling pathway including lipid metabolism on days 0, 4, 10, 21, 28 of differentiation.
Results: The main observation was significant increase of INSR, LIPE, FASN, SREBP1, OCT4 and AKT2 expression under influence of DDE. We did not record any increase of the active form of Akt.
Conclusion: Our findings suggest that DDE exposure changes the differentiation of adipocytes, enhances the lipid metabolism and so may play a role in the development of obesity and metabolic diseases by affecting the insulin signalling pathway. The influence of DDE seems to be similar to the effect of insulin itself. However, further studies to elucidate the mechanism of action of DDE are necessary.
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KEYWORD
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Adipocytes, Persistent organic pollutants, Dichlorodiphenyl dichloroethylene (DDE), Endocrine disruptor, Obesity
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