Prenatal Exposure to the Environmental Obesogen Tributyltin Predisposes Multipotent Stem Cells to Become Adipocytes
| العنوان: | Prenatal Exposure to the Environmental Obesogen Tributyltin Predisposes Multipotent Stem Cells to Become Adipocytes |
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| المؤلفون: | Séverine Kirchner, Bruce Blumberg, Tiffany Kieu, Connie Chow, Stephanie C. Casey |
| المصدر: | The Journal of Clinical Endocrinology & Metabolism. 95:982-982 |
| بيانات النشر: | The Endocrine Society, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Cellular differentiation, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, Peroxisome proliferator-activated receptor, White adipose tissue, Biology, Retinoid X receptor, Polymerase Chain Reaction, Biochemistry, Article, Mice, Endocrinology, Pregnancy, Internal medicine, Adipocytes, medicine, Animals, Humans, Molecular Biology, Cells, Cultured, Cell Proliferation, chemistry.chemical_classification, Multipotent Stem Cells, Biochemistry (medical), Cell Differentiation, General Medicine, Flow Cytometry, Mice, Inbred C57BL, chemistry, Adipogenesis, Multipotent Stem Cell, Female, Trialkyltin Compounds, Stem cell, Obesogen |
| الوصف: | The environmental obesogen hypothesis proposes that pre- and postnatal exposure to environmental chemicals contributes to adipogenesis and the development of obesity. Tributyltin (TBT) is an agonist of both retinoid X receptor (RXR) and peroxisome proliferator-activated receptor γ (PPARγ). Activation of these receptors can elevate adipose mass in adult mice exposed to the chemical in utero. Here we show that TBT sensitizes human and mouse multipotent stromal stem cells derived from white adipose tissue [adipose-derived stromal stem cells (ADSCs)] to undergo adipogenesis. In vitro exposure to TBT, or the PPARγ activator rosiglitazone increases adipogenesis, cellular lipid content, and expression of adipogenic genes. The adipogenic effects of TBT and rosiglitazone were blocked by the addition of PPARγ antagonists, suggesting that activation of PPARγ mediates the effect of both compounds on adipogenesis. ADSCs from mice exposed to TBT in utero showed increased adipogenic capacity and reduced osteogenic capacity with enhanced lipid accumulation in response to adipogenic induction. ADSCs retrieved from animals exposed to TBT in utero showed increased expression of PPARγ target genes such as the early adipogenic differentiation gene marker fatty acid-binding protein 4 and hypomethylation of the promoter/enhancer region of the fatty acid-binding protein 4 locus. Hence, TBT alters the stem cell compartment by sensitizing multipotent stromal stem cells to differentiate into adipocytes, an effect that could likely increase adipose mass over time. |
| تدمد: | 1945-7197 0021-972X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::036923fe368ddd36899b917a576522b1 https://doi.org/10.1210/jcem.95.2.9994 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....036923fe368ddd36899b917a576522b1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457197 0021972X |
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