The brominated flame retardant PBDE 99 promotes adipogenesis via regulating mitotic clonal expansion and PPAR7 expression

摘要

"Obesogens" have been widely accepted as chemicals that promote obesity, and there are many environmental pollutants that were functionally identified as obesogens. PBDE 99 is one of the most abundant PBDE congeners detected in human. However, its obesogenic effects are poorly understood. Here, we explore the in vitro effects of PBDE 99 on adipogenesis, which is a key process in obesogenesis. We observed an increase in adipogenesis when differentiating cells were exposed to PBDE 99. Further, the promoting effects of PBDE 99 on adipogenesis were most efficient during the first 4 days of 313-L1 differentiation. Consistent with this, early transcriptional factor CCAAT/enhancer-binding proteins beta (C/EBP beta) was upregulated at Days 1 and 2 during differentiation, which is accompanied with the acceleration of mitotic clonal expansion (MCE) and the upregulation of terminal transcriptional factors C/EBP alpha and PPAR gamma 2 from Day 2 or Day 4. Additionally, bisulfite genomic sequencing analysis revealed that PBDE 99 decreased methylation status of the CpG sites at PPAR gamma promoter region. Collectively, these findings demonstrate that PBDE 99 may be a potential environmental obesogen by promoting adipogenesis through facilitating MCE progression at early differentiation stage and upregulating key adipogenic factor PPAR gamma 2 expression both in direct transcriptional and epigenetic regulation dependent manner. (C) 2019 Elsevier B.V. All rights reserved.