Aldehoff Alix Sarah, Karkossa Isabel, Broghammer Helen, Krupka Sontje, Weiner Juliane, Goerdeler Cornelius, Nuwayhid Rima, Langer Stefan, Wabitsch Martin, Rolle-Kampczyk Ulrike, Klöting Nora, Blüher Matthias, Heiker John T, von Bergen Martin, Schubert Kristin
Department of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH (UFZ), Leipzig 04318, Germany.
Helmholtz Institute for Metabolic, Obesity and Vascular Research HI-MAG, Helmholtz-Centre Munich at the University of Leipzig and University Hospital, Leipzig 04103, Germany.
Environ Sci Technol. 2025 Aug 12;59(31):16193-16216. doi: 10.1021/acs.est.5c01206. Epub 2025 Jul 30.
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 model, and 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.
通过接触化学物质导致代谢紊乱的概念，拓展了我们对于环境污染如何导致代谢失调并最终引发肥胖等疾病的理解。我们需要评估化学物质所带来风险的新策略，而包括蛋白质组学在内的组学技术，已被证明是研究这些代谢干扰化学物质（MDCs）分子机制的有力工具。一种潜在的MDC是增塑剂 DINCH，它是DEHP等传统邻苯二甲酸盐的替代品，其主要代谢产物MINCH与脂肪生成和脂质积累的诱导有关。在这里，通过对蛋白质热稳定性以及翻译后修饰（PTM）乙酰化和磷酸化概况的深入了解，对全球蛋白质组学进行补充，从而深入理解化学物质诱导的脂肪细胞代谢紊乱。我们通过使用人类SGBS脂肪细胞系，证明了先进蛋白质组学方法在评估潜在MDCs效应方面的实用性。将来自饮食中接触DINCH的小鼠的脂肪组织PTM数据作为一个模型进行评估，这些数据揭示了DINCH的分子效应，包括其主要靶点PPARγ之外的蛋白质相互作用。结果强调了组学方法在加强当前新兴污染物风险评估框架方面的潜力。
