Development of a Three-Dimensional Adipose Tissue Model for Studying Embryonic Exposures to Obesogenic Chemicals.
Obesity is a rising issue especially in the United States that can lead to heart problems, type II diabetes, and respiratory problems. Since the 1970s, obesity rates in the United States have more than doubled in adults and children. Recent evidence suggests that exposure to certain chemicals, termed "obesogens," in utero may alter metabolic processes, predisposing individuals to weight gain. There is a need to develop a three-dimensional human tissue system that is able to model the effects of obesogens in vitro in order to better understand the impact of obesogens on early development. Human embryonic-derived stem cells in three-dimensional collagen embedded silk scaffolds were exposed to three different obesogens: Bisphenol A (BPA), Bisphenol S (BPS), and Tributyltin (TBT). The exposed tissues accumulated triglycerides and increased expression of adipogenic genes (Perilipin (PLIN1), peroxisome proliferator-activated receptor gamma (PPARy), fatty acid binding protein 4 (FABP4)) compared to equivalent control cultures with no obesogen exposure. These cultures were also compared to human adult stem cell cultures, which did not respond the same upon addition of obesogens. These results demonstrate the successful development of a representative tissue model of in utero obesogen exposures. This tissue system could be used to determine mechanisms of action of current obesogens and to screen other potential obesogens.
Biomedical Engineering, Tufts University, 4 Colby St., Medford, MA, 02155, USA.
Rebecca Y
RY
Wang
Biomedical Engineering, Tufts University, 4 Colby St., Medford, MA, 02155, USA.
Rosalyn D
RD
Abbott
Biomedical Engineering, Tufts University, 4 Colby St., Medford, MA, 02155, USA.
Adam
A
Zieba
Biomedical Engineering, Tufts University, 4 Colby St., Medford, MA, 02155, USA.
Francis E
FE
Borowsky
Biomedical Engineering, Tufts University, 4 Colby St., Medford, MA, 02155, USA. David.Kaplan@tufts.edu.
David L
DL
Kaplan
D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D005260:Female; D000066449:Human Embryonic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D013450:Sulfones / Q000633:toxicity*; D014220:Trialkyltin Compounds / Q000633:toxicity*; D000098831:Bisphenol S Compounds; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D010636:Phenols; D013450:Sulfones; D014220:Trialkyltin Compounds; C011559:tributyltin; C543008:bisphenol S; D000098831:Bisphenol S Compounds; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Adipocytes; Bisphenol-A; Bisphenol-S; Obesity; Obesogens; Scaffold; Silk; Tributyltin Chloride