Targeted and non-targeted lipidomic analysis of adipose tissue from general population to identify metabolic perturbations related to phthalate exposure
LABERCA, Oniris, INRAE -Nantes, FRANCE
Résumé
Adipose tissue dysfunction plays a relevant role in metabolic disorders, however few studies have applied lipidomic analysis to explore the potential associations between environmental chemicals and dysfunctional phenotypes. The objective of this study was to develop and apply a lipidomic workflow to explore the associations between exposure to phthalates and altered lipid profiles in adipose tissue of general population. For the present study, 81 individuals undergoing non-cancer related surgery from the GRAMO cohort (Spain) were included. Adipose tissue metabolites and lipids were extracted and two approaches were performed: a targeted study with Biocrates p180 kit and an untargeted lipidomic using a LC-Q-Exactive. Data were processed with Galaxy W4M. Phthalate metabolite levels in serum were measured by isotope diluted online-TurboFlow-LC-MS/MS with preceding enzymatic de-conjugation. Statistical analysis included partial least squares discriminatory analysis (PLS-DA) models and variable importance in the projection (VIP) was used for select those metabolites with a relative importance in the prediction model. In the multivariable regression models, concentrations of each phthalate were natural log-transformed in order to relax the linearity assumption. Models were adjusted for age and sex. The non-targeted analysis in positive mode provided 3735 features, 2917 of which were retained in the statistical analysis which showed 120 features statistically associated with the levels of the sum of phthalates (∑MxBP), 34 of which were successfully annotated. 216 targeted lipids were significantly associated with the phthalates levels. These preliminary analyses support that exposure to low molecular phthalates may be related to a specific metabolic profile in adipose tissue.
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