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Metabolomics in human SGBS cells as new approach method for studying adipogenic effects: Analysis of the effects of DINCH and MINCH on central carbon metabolism.
Goerdeler, Cornelius; Engelmann, Beatrice; Aldehoff, Alix Sarah; Schaffert, Alexandra; Blüher, Matthias; Heiker, John T; Wabitsch, Martin; Schubert, Kristin; Rolle-Kampczyk, Ulrike; von Bergen, Martin.
Afiliación
  • Goerdeler C; Department of Molecular Toxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany. Electronic address: cornelius.goerdeler@ufz.de.
  • Engelmann B; Department of Molecular Toxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany. Electronic address: beatrice.engelmann@ufz.de.
  • Aldehoff AS; Department of Molecular Toxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany. Electronic address: alix-sarah.aldehoff@ufz.de.
  • Schaffert A; Department of Molecular Toxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany. Electronic address: alexandra.schaffert@i-med.ac.at.
  • Blüher M; Department of Endocrinology, Nephrology and Rheumatology, Faculty of Medicine, University of Leipzig, Leipzig, Germany; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Ge
  • Heiker JT; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany. Electronic address: john.heiker@helmholtz-muenchen.de.
  • Wabitsch M; Division of Pediatric Endocrinology and Diabetes, Ulm University Medical Center, Ulm, Germany. Electronic address: Martin.Wabitsch@uniklinik-ulm.de.
  • Schubert K; Department of Molecular Toxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany. Electronic address: kristin.schubert@ufz.de.
  • Rolle-Kampczyk U; Department of Molecular Toxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany. Electronic address: ulrike.rolle-kampczyk@ufz.de.
  • von Bergen M; Department of Molecular Toxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany; Institute of Biochemistry, Leipzig University, Leipzig, Germany; German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany. Electronic address: martin.vonber
Environ Res ; 252(Pt 2): 118847, 2024 Jul 01.
Article en En | MEDLINE | ID: mdl-38582427
ABSTRACT
Growing evidence suggests that exposure to certain metabolism-disrupting chemicals (MDCs), such as the phthalate plasticizer DEHP, might promote obesity in humans, contributing to the spread of this global health problem. Due to the restriction on the use of phthalates, there has been a shift to safer declared substitutes, including the plasticizer diisononyl-cyclohexane-1,2-dicarboxylate (DINCH). Notwithstanding, recent studies suggest that the primary metabolite monoisononyl-cyclohexane-1,2-dicarboxylic acid ester (MINCH), induces differentiation of human adipocytes and affects enzyme levels of key metabolic pathways. Given the lack of methods for assessing metabolism-disrupting effects of chemicals on adipose tissue, we used metabolomics to analyze human SGSB cells exposed to DINCH or MINCH. Concentration analysis of DINCH and MINCH revealed that uptake of MINCH in preadipocytes was associated with increased lipid accumulation during adipogenesis. Although we also observed intracellular uptake for DINCH, the solubility of DINCH in cell culture medium was limited, hampering the analysis of possible effects in the µM concentration range. Metabolomics revealed that MINCH induces lipid accumulation similar to peroxisome proliferator-activated receptor gamma (PPARG)-agonist rosiglitazone through upregulation of the pyruvate cycle, which was recently identified as a key driver of de novo lipogenesis. Analysis of the metabolome in the presence of the PPARG-inhibitor GW9662 indicated that the effect of MINCH on metabolism was mediated at least partly by a PPARG-independent mechanism. However, all effects of MINCH were only observed at high concentrations of 10 µM, which are three orders of magnitudes higher than the current concentrations of plasticizers in human serum. Overall, the assessment of the effects of DINCH and MINCH on SGBS cells by metabolomics revealed no adipogenic potential at physiologically relevant concentrations. This finding aligns with previous in vivo studies and supports the potential of our method as a New Approach Method (NAM) for the assessment of adipogenic effects of environmental chemicals.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adipocitos / Ácidos Ciclohexanocarboxílicos / Ácidos Dicarboxílicos / Adipogénesis / Metabolómica Límite: Humans Idioma: En Revista: Environ Res Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adipocitos / Ácidos Ciclohexanocarboxílicos / Ácidos Dicarboxílicos / Adipogénesis / Metabolómica Límite: Humans Idioma: En Revista: Environ Res Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos