Mixtures of p,p′-DDE, PCB153, BDE47, and PFOS Alter Adipocytic Differentiation of 3T3-L1 Cells

Exposure to certain chemicals can promote adipogenesis, but less is known about whether exposure to human-relevant chemical mixtures behaves similarly. Chemical concentrations from the serum of mothers enrolled in the Environmental Influences on Child Health Outcomes-Fetal Growth Study (n = 813) were used in a self-organizing map algorithm to identify five distinct patterns of real-world exposure mixtures containing <i>p</i>,<i>p</i>'-DDE, PCB153, BDE47, and PFOS. Each mixture profile was exposed to 3T3-L1 cells at 1×, 50×, and 500× serum levels over a 14-day adipogenic differentiation period. Cells were assessed for triglycerides and markers of adipocyte formation and maturation. The results indicate that a mixture dominated by high BDE47 levels (Profile 3) behaved differently than BDE47 alone. BDE47 alone increased expression of <i>Fsp27</i>, <i>Fabp4</i>, and <i>Cpt1</i>, while the Profile 3 mixture inhibited expression of these three genes. In contrast, mixtures dominated by either <i>p</i>,<i>p</i>'-DDE or PFOS (Profiles 1 and 4) behaved similarly to their dominant chemicals. Exposures inducing Pparγ increased <i>Fsp27</i> levels, while those inducing Ampk reduced <i>Fsp27</i> levels. These findings suggest that individual chemicals alter transcription factors that control adipogenesis, and the interplay between transcription factors yields synergistic or antagonistic chemical interactions in real-world mixture exposures.