Lipogenic Potency of Individual Perfluorinated Alkyl Acids (PFAAs) and Persistent Organic Pollutant (POP) Mixtures at Human Blood-Based Exposure Levels on Adipogenesis in 3T3-L1 Cells

Background In recent decades, the incidence of metabolic disorders has increased internationally. This increase has been linked to exposure to persistent organic pollutants (POPs) but little is known about the metabolic effects of realistic human exposure mixtures at relevant concentrations. Objectives In this study we tested if POPs, representing real life exposure profiles and concentrations, were able to disrupt development and functions of adipose tissue in a direct way. Methods The lipogenic potency of a POP mixture modelled on levels found in human blood as detected in the Scandinavian population was assessed. The Total mixture comprises 29 compounds divided over three groups: chlorinated (Cl), brominated (Br), and perfluorinated compounds (PFAA). Individual PFAA chemicals, the Total mixture, and sub-mixtures (Cl, Br, PFAA, Cl + Br, Cl + PFAA, and Br + PFAA) at five (× 1/10, × 1, × 50, × 100, and × 500) human blood levels were tested in an optimised high content analysis (HCA) 3T3-L1 adipogenesis assay. Results Individual PFAAs; perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) promoted lipid accumulation in 3T3-L1 cells. The Total mixture, and the Cl, PFAA, Cl + Br, and Cl + PFAA sub-mixtures, promoted adipogenic differentiation and lipid accumulation. Increased lipid accumulation promoted adipose tissue expansion. Conclusions To the authors knowledge, this is the first in vitro bioassay study assessing the adipogenic effects of POP mixtures modelled on real-life human exposure levels. The findings highlight that such exposures may alter adipose tissue development and function, thus potentially playing a role in the globally increasing escalation of metabolic disorders.