Benzyl butyl phthalate induces epigenetic stress to enhance adipogenesis in mesenchymal stem cells. Academic Article uri icon

abstract

  • Endocrine disruptors, phthalates, may have contributed to recent global obesity health crisis. Our study investigated the potential of benzyl butyl phthalate (BBP) to regulate the mesenchymal stem cell epigenome to drive adipogenesis. BBP exposure enhanced lipid accumulation and adipogenesis in a dose-dependent manner compared to control (P<0.001). Adipogenesis markers, PPAR (P<0.001), C/EBP (P<0.01), and aP2 (P<0.001) were significantly upregulated by increasing concentrations of BBP when compared to DMSO. BBP enhanced H3K9 acetylation while decreasing H3K9 dimethylation. Fifty M BBP increased histone acetyltransferases, p300 (P<0.05) and GCN5 (P<0.01) gene expression. Furthermore, histone deacetylases (HDACs), HDAC3 (P<0.01) and HDAC10 (P<0.01, 10M BBP; P<0.001, 50M BBP) and histone methyltransferases, SETDB1 (P<0.01) and G9a (P<0.01), were significantly downregulated by BBP exposure. BBP acts, in part, through PPAR, as PPAR knockdown led to decreased H3K9ac and rescued H3K9me2 during BBP exposure. In conclusion, BBP regulated MSCs towards adipogenesis by tipping the epigenomic balance.

published proceedings

  • Mol Cell Endocrinol

altmetric score

  • 79.48

author list (cited authors)

  • Sonkar, R., Powell, C. A., & Choudhury, M.

citation count

  • 40

complete list of authors

  • Sonkar, Ravi||Powell, Catherine A||Choudhury, Mahua

publication date

  • August 2016