Molecular mechanisms of vitamin D plus Bisphenol A effects on adipogenesis in human adipose-derived mesenchymal stem cells
Open Access
- 9 April 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Diabetology & Metabolic Syndrome
- Vol. 13 (1), 1-9
- https://doi.org/10.1186/s13098-021-00661-4
Abstract
Obesity is considered a major health concern and mounting evidence suggests that the exposure to environmental endocrine disruptors, including Bisphenol-A (BPA), may enhance the risk to develop the disease. Moreover, growing documents propose that the vitamin D may contribute to adipogenic signaling and lipid accumulation during adipocyte differentiation. We focused on the molecular mechanism of vitamin D and BPA in human adipose-derived mesenchymal stem cells (hADMSCs) which vitamin D and BPA may influence adipose tissue development and function. Human adipose-derived mesenchymal stem cells were cultured for 14 days in lipogenic differentiation media containing continuous concentrations of vitamin D plus BPA (0.1 nM or 10 nM). The expression of adipogenic markers including the peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBP α) CCAAT-enhancer-binding protein β (C/EBP β), fatty acid synthase (FASN), lipoprotein lipase (LPL), sterol regulatory element-binding protein-1c (SREBP1c), insulin-induced gene-2 (INSIG2), vitamin D receptor (VDR), estrogen receptor-beta (ER-β), fatty acid-binding protein-4 (FABP4), and glucose transporter-4 (GLUT4) was measured using Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Lipid accumulation was visualized with staining with Oil Red O. In the morphological assessment of mesenchymal stem cells treated with a concentration of 10 nM vitamin D plus BPA, more lipid accumulations were observed in comparison with the group with 0.1 nM concentration. Treatment of hADMSCs with vitamin D plus BPA (0.1 nM) significantly inhibited the induction of PPARγ, C/EBP β, C/EBP α, and FASN related to adipocyte differentiation and development. However, the exposure of cells to the concentration of 10 nM vitamin D plus BPA induced the expression of these genes associated to the adipogenesis. The remarkable increase in the level of SREBP1c was associated to the suppression of INSIG2 in treated preadipocytes with 10 nM vitamin D plus BPA. Our findings showed that the expression of VDR, ERβ, GLUT4, and FABP4 were upregulated through differentiation with the highest concentrations in 0.1 nM vitamin D plus BPA group for VDR, ERβ, and GLUT4. Vitamin D plus BPA at concentration of 10 nM boosted the adipogenesis during the critical stages of adipocytes development, whereas it seems to inhibit this process at concentration of 0.1 nM.Keywords
Funding Information
- Iran University of Medical Sciences (27697)
- Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences (96044)
This publication has 37 references indexed in Scilit:
- The beneficial role of vitamin D in obesity: possible genetic and cell signaling mechanismsNutrition Journal, 2013
- 25-Hydroxyvitamin D3 and 1,25-Dihydroxyvitamin D3 Promote the Differentiation of Human Subcutaneous PreadipocytesPLOS ONE, 2012
- The Fat Controller: Adipocyte DevelopmentPLoS Biology, 2012
- AdipogenesisCold Spring Harbor Perspectives in Biology, 2012
- Bisphenol A Diglycidyl Ether Induces Adipogenic Differentiation of Multipotent Stromal Stem Cells through a Peroxisome Proliferator–Activated Receptor Gamma-Independent MechanismEnvironmental Health Perspectives, 2012
- Differential Estrogenic Actions of Endocrine-Disrupting Chemicals Bisphenol A, Bisphenol AF, and Zearalenone through Estrogen Receptor α and β in VitroEnvironmental Health Perspectives, 2012
- Bisphenol A-Mediated Suppression of LPL Gene Expression Inhibits Triglyceride Accumulation during Adipogenic Differentiation of Human Adult Stem CellsPLOS ONE, 2012
- Targeted Expression of Human Vitamin D Receptor in Adipocytes Decreases Energy Expenditure and Induces Obesity in MiceJournal of Biological Chemistry, 2011
- Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteinsAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- CCAAT/enhancer-binding protein β is required for mitotic clonal expansion during adipogenesisProceedings of the National Academy of Sciences of the United States of America, 2003