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Aldehoff, A.S.* ; Karkossa, I.* ; Broghammer, H. ; Krupka, S. ; Weiner, J. ; Goerdeler, C.* ; Nuwayhid, R.* ; Langer, S.* ; Wabitsch, M.* ; Rolle-Kampczyk, U.* ; Klöting, N. ; Blüher, M. ; Heiker, J.T. ; von Bergen, M.* ; Schubert, K.*

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.

Environ. Sci. Technol., 24 (2025)

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	Open Access Gold (Paid Option)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Dinch ; Minch ; Acetylation ; Adipocytes ; Adipose Tissue ; Metabolic Disruption ; Phosphorylation ; Thermal Proteome Profiling; Activated Protein-kinases; Adipose-tissue; Ppar-gamma; Differentiation; Adipocytes; Identification; Inflammation; Endocrine; Alpha

ISSN (print) / ISBN 0013-936X

e-ISSN 1520-5851

Journal Environmental Science & Technology

Quellenangaben Pages: 24

Publisher ACS

Publishing Place Washington, DC

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants German Research Foundation for the Collaborative Research Centre "Obesity Mechanisms"
German Research Foundation
Doctoral scholarship of the "Studienstiftung des Deutschen Volkes"
European Union
UFZ
Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF) as part of the German Center for Child and Adolescent Health (DZKJ)