Publication Details |
| Category | Text Publication |
| Reference Category | Preprints |
| DOI | 10.2139/ssrn.5342656 |
| Title (Primary) | 13C metabolic tracing in human SGBS cells provides a potential new approach methodology for assessing metabolism-disrupting properties of environmental chemicals |
| Author | Goerdeler, C.; Engelmann, B.; Broghammer, H.; Aldehoff, A.S.; Wabitsch, M.; Schubert, K.; Blüher, M.; Heiker, J.T.; Rolle-Kampczyk, U.; von Bergen, M. |
| Source Titel | SSRN |
| Year | 2025 |
| Department | iDiv; MOLTOX |
| Language | 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. |
| Persistent UFZ Identifier | 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 |
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