Advanced Proteomics Approaches Hold Potential for the Risk Assessment of Metabolism-Disrupting Chemicals as Omics-Based NAM: A Case Study Using the Phthalate Substitute DINCH

The concept of metabolic disruption through exposure
to chemicals
has expanded our understanding of how environmental pollution can
contribute to metabolic dysregulation and, ultimately, diseases like
obesity. New strategies for assessing the risks posed by chemicals
are needed, and omics technologies, including proteomics, have proven
to be powerful tools for investigating the molecular mechanisms of
these metabolism-disrupting chemicals (MDCs). A potential MDC is the
plasticizer DINCHan alternative to legacy phthalates like
DEHP, whose primary metabolite MINCH has been linked to the induction
of adipogenesis and lipid accumulation. Here, global proteomics was
complemented with insights into protein thermal stability and the
profiles of post-translational modification (PTM) acetylation and
phosphorylation to provide a profound understanding of chemical-induced
metabolic disruption in adipocytes. We demonstrate the utility of
advanced proteomics approaches in assessing the effects of potential
MDCs by using the human SGBS adipocyte cell line. Adipose tissue PTM
data from dietary DINCH-exposed mice were assessed as an in
vivo model, and in vitro data shed light
on DINCH’s molecular effects, including protein interactions
beyond its primary target PPARγ. The results emphasize the potential
of omics approaches to enhance current risk assessment frameworks
for emerging contaminants.