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.
Highlights
Les CLA font l’objet d’une recherche intense depuis le debut des annees 1990, notamment pour evaluer les modalites de leur effet anti-obesite (Roche et al, 2001)
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/
Summary
Les CLA font l’objet d’une recherche intense depuis le debut des annees 1990, notamment pour evaluer les modalites de leur effet anti-obesite (Roche et al, 2001). Si cette activite est bien documentee et averee dans certains modeles animaux (souris (West et al, 1998), hamsters (Navarro et al, 2009), rats genetiquement obeses (Kelley et Erickson, 2003), en revanche les effets sont plus tenus et controverses chez l’humain (Whigham et al, 2007). Certains pointent un risque d’aggraver le syndrome metabolique chez des sujets consommant des preparations contenant l’isomere t10,c12 et chez qui ce syndrome preexiste (Riserus et al, 2002). Nous avons choisi d’evaluer le retentissement biologique de la consommation de CLA contenant l’isomere t10,c12 sur des adipocytes humains sous-cutanes en culture, le tissu adipeux etant une cible majeure pour les CLA dans le cadre des effets anti-obesite et d’insulino-resistance.
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