Proposal of a bioinformatics approach to predict molecular mechanisms involved in inflammatory response: case of ATRA and 1,25(OH)2D in adipocytes

Abstract

Several inflammatory markers such as cytokines, chemokines, and microRNAs (miRNAs) are well known to be induced during obesity and are strongly linked to their comorbidities. Among many others factors, the micronutrient status is suspected to reduce obesity-associated inflammation via blunting inflammatory signalling pathways. This is notably the case for active forms of vitamin A (all-trans retinoic acid ATRA) and vitamin D (1,25(OH)2D) as previously shown. In the present study, we aimed to implement a new bioinformatics approach to unveil commonly regulated signalling pathways through a combination of gene and miRNA expression sets impacted by ATRA and 1,25(OH)2D in adipocytes. In a first set of experiments, we focused only our attention on ATRA and demonstrated that it reduced LPS-mediated miRNA expression (miR-146a, miR-150, and miR-155) in mouse adipose tissue, in adipocyte cultures, and in adipocyte-derived vesicles. This result was confirmed in TNFα-induced miRNA in human adipocytes. Then, bioinformatic analysis highlighted that both ATRA and 1,25(OH)2D-regulated genes and miRNA converge to the canonical ‘nuclear factor Kappa B (NF-κB) signalling pathway.’ Altogether, these results showed that ATRA has anti-inflammatory effects on miRNA expression. In addition, the proposed bioinformatic model converges to NF-κB signalling pathway that has been previously demonstrated to be regulated by ATRA and 1,25(OH)2D, thus confirming the interest of such approach.