Évaluation de l’exposition d’adipocytes humains sous-cutanés en culture aux acides linoléiques conjugués par une approche multi-omique

Abstract

Conjugated linoleic acids are 18 carbones fatty acids members comprising a consecutive (conjugated) double bonds system with a various cis/trans geometry sequence, giving rise to at least 16 different isomers. Among those, the t10,c12 isomer has been reported to have anti-obesity properties. We evaluated the biological response of human primary adipose tissue cultured adipocytes to that CLA isomer, alone or present in a commercial mixture, using system biology approaches (primarily transcriptomics and metabolomics). We found that CLA changed the biological activity of at least 45 metabolic pathways at the genomic level, which transcriptional activities was associated to a parallelle metabolome adipocyte change (lipidome upmost) (r2value transcriptome/ metabolome of 0.89). In pairwise analysis, it appeared that 6 of these pathways at the genomic level were tightly associated to the metabolomic response, such as apoptosis, interleukine-6, proteasome, reticulum endoplasmic stress, transcription role of heterochromatine, cell proliferation through EGFR dependent tyrosine kinase, gamma-aminobutyrate receptor. This latter exhibited the most tightly relationship with the metabolome variations in multivariated analysis. One may infer that this pathway is the most targeted by CLA treatment. In conclusion, the implementation of a multi-omic global approach allowed the identification of a set of biological pathways at the genomic level associated to the metabolic balance of CLA-treated adipocytes. All of these pathways are related to insulin-resistance, metabolic syndrome and adipogenesis.