Utilizing proteomic approaches to study the molecular effects of emerging plastic additives in human adipocytes

Bisphenol A (BPA) is well-known for its disruptive effects on the endocrine system, as well as the metabolism. Adipose tissue, beyond its role in energy storage, is also an important endocrine organ. BPA has been shown to alter insulin sensitivity, which can subsequently lead to the development of type 2 diabetes. Due to the classification of BPA as an endocrine disruptive chemical its use in many everyday consumer products has been restricted in the European Union. Consequently, novel BPA alternatives are now prevalent in various consumer products, and so is our exposure to these chemicals. The effects of these novel plastic additives on the endocrine system and metabolism remain poorly understood, rendering the hazard assessment and the understanding of their molecular modes of action in the adipose tissue extremely relevant.

Therefore, this research project aims to evaluate eight BPA alternatives of high concern for their impact on human adipocytes within the framework of the Partnership for the Assessment of Risk from Chemicals (PARC). Specifically, the analysis will focus on the critical endpoints such as lipid accumulation, cell toxicity, binding effects to cellular proteins, and alterations in the proteome.

The treatment of adipocytes with brominated bisphenols TBBPA (tetrabromobisphenol A) and TBBPS (tetrabromobisphenol S), commonly used as flame retardants, induced significant changes in the adipocyte"s lipid accumulation. This effect is mediated through interference with nuclear receptors responsible for adipocyte differentiation and was demonstrated at concentrations ranging from environmentally relevant to bioaccumulative concentrations. Simultaneously, the cytotoxic effects of the halogenated bisphenols were determined at higher concentrations. Additionally, we were able to use thermal proteome profiling to identify potential chemical-protein interactions. Preliminary results have shown a significant shift in melting points of proteins that are associated with stress response and lipid metabolism. Additionally, global proteome analysis was applied to give insights into the changes in protein abundance, thereby revealing disrupted signalling pathways and shedding light on their potential modes of action.

In conclusion, our findings could unveil molecular mechanisms triggered in human adipocytes and simultaneously aid in the hazard assessment, thereby supporting necessary restrictions for chemicals, humans and the environment are permanently exposed to. By comprehensively examining these various endpoints, our study seeks to elucidate the potential health risks posed by these novel plastic additives.