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MUCOSAL BIOLOGY

Transcriptome response of enterocytes to dietary lipids: impact on cell architecture, signaling, and metabolism genes

¹Université Pierre et Marie Curie-Paris 6, Les Cordeliers UMRS 872, Paris; ²Institut National de la Santé et de la Recherche Médicale U872, Paris; ³Université Paris Descartes UMRS 872, Paris; ⁴Sanofi-Aventis, DMPK-S, Discovery Metabolism, Pharmacokinetics and Safety Department, Montpellier; and ⁵Sanofi-Aventis, Oncology Department, Montpellier, France

Submitted 13 March 2008 ; accepted in final form 25 August 2008

Intestine contributes to lipid homeostasis through the absorption of dietary lipids, which reach the apical pole of enterocytes as micelles. The present study aimed to identify the specific impact of these dietary lipid-containing micelles on gene expression in enterocytes. We analyzed, by microarray, the modulation of gene expression in Caco-2/TC7 cells in response to different lipid supply conditions that reproduced either the permanent presence of albumin-bound lipids at the basal pole of enterocytes or the physiological delivery, at the apical pole, of lipid micelles, which differ in their composition during the interprandial (IPM) or the postprandial (PPM) state. These different conditions led to distinct gene expression profiles. We observed that, contrary to lipids supplied at the basal pole, apical lipid micelles modulated a large number of genes. Moreover, compared with the apical supply of IPM, PPM specifically impacted 46 genes from three major cell function categories: signal transduction, lipid metabolism, and cell adhesion/architecture. Results from this first large-scale analysis underline the importance of the mode and polarity of lipid delivery on enterocyte gene expression. They demonstrate specific and coordinated transcriptional effects of dietary lipid-containing micelles that could impact the structure and polarization of enterocytes and their functions in nutrient transfer.

nutrients; alimentary lipids; mRNA; intestine