Abstract
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. 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. 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 optimized high content analysis (HCA) 3T3-L1 adipogenesis assay. All exposures promoted adipocyte formation in 3T3-L1 cells at concentrations equivalent to × 1/10 human blood levels. PFAAs promoted lipid accumulation in 3T3-L1 cells at 33.6 pM (PFUnDA) and 390,460 pM (PFHxS). The Total mixture, and the Cl, PFAA, Cl + Br and Cl + PFAA sub-mixtures, started to promote lipid accumulation at × 1/10 human blood levels. This in vitro bioassay study assessed 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.
Highlights
Persistent organic pollutants (POPs) maintain a strong structural stability that enables them to persist for a long time in the environment and accumulate in biota (WHO/ UNEP 2013)
This study aimed to investigate the potential for POPs and their mixtures to disrupt adipogenesis at human relevant exposure levels, providing insight into alternative mechanisms by which POPs may be involved in the disruption of adipocyte development and pathogenesis of obesity and metabolic disorders
Increased adipogenesis and lipid accumulation may lead to impaired adipose tissue function and excessive fat storage in the body
Summary
Persistent organic pollutants (POPs) maintain a strong structural stability that enables them to persist for a long time in the environment and accumulate in biota (WHO/ UNEP 2013). White adipose tissue is an endocrine organ which stores excessive energy in the form of triacylglycerol, a neutral lipid. This lipid is held within lipid vacuoles in adipocytes, resulting in body fat accumulation. There is a need to study the metabolic disrupting effects of these chemicals at levels and mixtures representing real-life exposure. The breakdown and decrease of body fat can lead to the release and resulting increase in organochlorine pollutant plasma concentrations, indicating that adipose tissue can function as an in vivo exposure source of POPs (Bräuner et al 2011; De Roos et al 2012)
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