TY - JOUR
T1 - Exposure of adipocytes to bisphenol-A in vitro interferes with insulin action without enhancing adipogenesis
AU - De Filippis, Elena
AU - Li, Ting
AU - Rosen, Evan David
N1 - Funding Information:
EDF was supported by a grant from the Endocrine Fellowship Foundation, Fellows Development Research Grant Program in Diabetes, Obesity and Fat Cell Biology, and a T32 award. EDR is supported by NIH R01 DK102173, DK102170, DK113669, and DK085171. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank Zhang Xu and Su Xu for their technical assistance. We thank Sona Kang for sharing her cell culture knowledge with the authors and providing advice; Linus Tsai also provided significant intellectual support for this project. EDF was supported by a grant from the Endocrine Fellowship Foundation, Fellows Development Research Grant Program in Diabetes, Obesity and Fat Cell Biology, and a T32 award. EDR is supported by NIH R01 DK102173, DK102170, DK113669, and DK085171. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
WewouldliketothankZhangXuandSuXufortheirtechnicalassistance.WethankSona Kangforsharinghercellcultureknowledgewiththeauthorsandprovidingadvice;LinusTsai alsoprovidedsignificantintellectualsupportforthisproject.EDFwassupportedbyagrant from the Endocrine Fellowship Foundation, F ellows Developmen t Resear ch Gr an t Progr am in Dia betes, Obesity and F a t CellBiology, and a T32 award. EDR is supported by NIH R01 DK102173,DK102170,DK113669,andDK085171.Thefundershadnoroleinstudydesign, datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript.
Publisher Copyright:
© 2018 De Filippis et al. 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 credited.
PY - 2018/8
Y1 - 2018/8
N2 - Bisphenol-A (BPA) is a lipophilic compound widely used in the manufacture of plastic items and thought to play a role in the growing obesity epidemic. Recent publications suggest that BPA may have a pro-adipogenic effect. Here we explore the effect of low, but environmentally relevant, concentrations of BPA on adipogenesis using a variety of cellular models. Mouse 3T3-L1, C3H10T1/2 and human adipose-derived stromal cells (hADSCs) were cultured with BPA concentrations ranging from 0.1nM to 100μM. We failed to observe positive effects on differentiation at any dose or in any model. 3T3-L1 adipocytes differentiated with high concentrations of BPA showed decreased mRNA expression of several adipocyte markers. Mature adipocytes differentiated in the presence of BPA were insulin resistant, with an approximate 25% reduction in insulin-stimulated glucose uptake. This was accompanied by a significant decrease in insulin-stimulated Akt phosphorylation, and an increase in mRNA levels of inflammatory markers (i.e. IL-6, TNFα). In conclusion, low, but environmentally relevant, doses of BPA may contribute to the development of a chronic, low-grade inflammatory state in exposed adipocytes, which in turn may affect adipose tissue insulin sensitivity, independent of adipogenesis. These studies suggest an alternative mechanism by which BPA may contribute to the development of obesity.
AB - Bisphenol-A (BPA) is a lipophilic compound widely used in the manufacture of plastic items and thought to play a role in the growing obesity epidemic. Recent publications suggest that BPA may have a pro-adipogenic effect. Here we explore the effect of low, but environmentally relevant, concentrations of BPA on adipogenesis using a variety of cellular models. Mouse 3T3-L1, C3H10T1/2 and human adipose-derived stromal cells (hADSCs) were cultured with BPA concentrations ranging from 0.1nM to 100μM. We failed to observe positive effects on differentiation at any dose or in any model. 3T3-L1 adipocytes differentiated with high concentrations of BPA showed decreased mRNA expression of several adipocyte markers. Mature adipocytes differentiated in the presence of BPA were insulin resistant, with an approximate 25% reduction in insulin-stimulated glucose uptake. This was accompanied by a significant decrease in insulin-stimulated Akt phosphorylation, and an increase in mRNA levels of inflammatory markers (i.e. IL-6, TNFα). In conclusion, low, but environmentally relevant, doses of BPA may contribute to the development of a chronic, low-grade inflammatory state in exposed adipocytes, which in turn may affect adipose tissue insulin sensitivity, independent of adipogenesis. These studies suggest an alternative mechanism by which BPA may contribute to the development of obesity.
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U2 - 10.1371/journal.pone.0201122
DO - 10.1371/journal.pone.0201122
M3 - Article
C2 - 30133442
AN - SCOPUS:85052147202
SN - 1932-6203
VL - 13
JO - PLoS One
JF - PLoS One
IS - 8
M1 - e0201122
ER -