Details zur Publikation
Kategorie Textpublikation
Referenztyp Preprints
DOI 10.2139/ssrn.5342656
Titel (primär) 13C metabolic tracing in human SGBS cells provides a potential new approach methodology for assessing metabolism-disrupting properties of environmental chemicals
Autor Goerdeler, C.; Engelmann, B.; Broghammer, H.; Aldehoff, A.S.; Wabitsch, M.; Schubert, K.; Blüher, M.; Heiker, J.T.; Rolle-Kampczyk, U.; von Bergen, M.
Quelle SSRN
Erscheinungsjahr 2025
Department iDiv; MOLTOX
Sprache englisch
Topic T9 Healthy Planet
Abstract Human exposure to certain environmental chemicals, including phthalates, is linked to metabolic disruption and may thereby contribute to diseases like obesity. However, regulatory methods to evaluate such effects are currently lacking. DINCH was introduced as a substitute for banned phthalate plasticizers, but its primary metabolite, MINCH, has been shown to promote adipogenesis in human preadipocytes and alter the lipid metabolism of mature adipocytes. To investigate its potential metabolism-disrupting effects, we assessed changes in the central carbon metabolism activity of human preadipocytes and mature adipocytes by 13C metabolic tracing. In preadipocytes, MINCH increased glycolysis, pentose phosphate pathway activity, acetyl-CoA production from glucose and glutamine, and pyruvate anaplerosis, indicating a metabolic shift toward adipogenesis. In mature adipocytes, MINCH enhanced glycolysis, glyceroneogenesis, fatty acid oxidation, and oxidative TCA cycle activity, pathways associated with the browning of adipocytes. Elevated UCP1 expression confirmed MINCH-induced browning. While MINCH-induced changes mainly mirrored those of the PPARg agonist rosiglitazone, ¹³C tracing revealed minor pathway activity differences, supporting partly PPARg-independent effects. Although most effects occurred at micromolar concentrations, subtle changes were already observed at nanomolar concentrations in preadipocytes. Overall, our findings demonstrate the utility of 13C metabolic tracing as a sensitive New Approach Methodology for chemical risk assessment.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=31097
Goerdeler, C., Engelmann, B., Broghammer, H., Aldehoff, A.S., Wabitsch, M., Schubert, K., Blüher, M., Heiker, J.T., Rolle-Kampczyk, U., von Bergen, M. (2025):
13C metabolic tracing in human SGBS cells provides a potential new approach methodology for assessing metabolism-disrupting properties of environmental chemicals
SSRN 10.2139/ssrn.5342656