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 p,p'-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 Fsp27, Fabp4, and Cpt1, while the Profile 3 mixture inhibited expression of these three genes. In contrast, mixtures dominated by either p,p'-DDE or PFOS (Profiles 1 and 4) behaved similarly to their dominant chemicals. Exposures inducing Pparγ increased Fsp27 levels, while those inducing Ampk reduced Fsp27 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.