Defining the role of 2,2',4,4'-tetrabromodiphenyl ether in 3T3-L1 cellular differentiation by transcriptome sequencing analysis

Adipocyte. 2024 Dec;13(1):2430717. doi: 10.1080/21623945.2024.2430717. Epub 2024 Dec 7.

Abstract

This study aims to investigates the effect of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on the differentiation of 3T3-L1 cells and its mechanism of action. These 3T3-L1 cells were induced to differentiate in vitro using methylisobutylxanthine, dexamethasone, and insulin conditions, then exposed to either 1% DMSO as a control group or varying concentrations of BDE-47 (2.5 μM, 7.5 μM, 12.5 μM, 18.75 μM, and 25 μM). Oil red O staining showed that the absorbance value of the BDE-47 exposure groups was higher than that of the control group (p < 0.05). This study identified 722 common genes between the differentially expressed genes of each exposure group. Using Cytoscape 10 hub genes were identified as Actb, Cdk1, Myc, Ccnb1, Aurkb, Plk1, Aurka, Pparg, Kif11, and Casp3. Enrichment analysis data revealed that the effects of BDE-47 on 3T3-L1 cell differentiation were associated with the cell cycle, p53 signalling, and PPARγ pathways. The transcription factor genes, KAT2A, MAX, SIN3A, TBP, and EP300, were shown to be associated with the PPARγ pathway. The mRNA expression of PPARγ in each exposure group was higher than that in the control group (p < 0.05), and a bimodal distribution between PPARγ mRNA expression and BDE-47 dose was observed. These findings indicate that BDE-47 May activate the PPARγ pathway and mitotic pathway to regulate the cell cycle and induce adipocyte differentiation.

Keywords: 3T3-L1; BDE-47; adipogenesis; mitosis; transcriptome sequencing.

MeSH terms

  • 3T3-L1 Cells*
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Animals
  • Cell Differentiation* / drug effects
  • Gene Expression Profiling
  • Halogenated Diphenyl Ethers* / pharmacology
  • Mice
  • Transcriptome

Substances

  • Halogenated Diphenyl Ethers
  • 2,2',4,4'-tetrabromodiphenyl ether

Grants and funding

This article was supported by the National Natural Science Foundation of China (Grant Nos. 82160605 and 81760596) and the 14th Five-Year Plan Distinctive Program of Public Health and Preventive Medicine in Higher Education, Institutions of Xinjiang Uygur Autonomous Region.