Changes In Liver Fatty Acid Binding Protein Expression Modifies Fatty Acid Metabolism, Growing And Differentiation Of Caco-2 Cells

FALOMIR LOCKHART LJ; RODRIGUEZ SAWICKI, L; FRANCHINI GR; STORCH J; CÓRSICO

Maastricht

Congreso; 9th ISSFAL Meeting - Maastricht 2010; 2010

ISSFAL - University of Maastricht

Background: The intestinal epithelium assimilates and processes a large quantity of lipids incorporated with the diet. They are absorbed mainly as free fatty acids (FA) and sterols, and as monoacylglicerols; to be then reesterified inside the enterocytes, assembled and secreted as Quilomicrons into the lymph. This type of cells express large quantities of two Fatty Acid Binding Proteins (FABP): intestinal FABP (IFABP) and liver FABP (LFABP), which are suggested to be cytosolic buffers and/or transporters for hydrophobic ligands. Nevertheless, new functions have been recently proposed related to control of gene expression and cell differentiation. Objective: To evaluate LFABP´s role in the lipid metabolism and cell biology of the enterocyte, employing a cellular model of Caco-2 cells with ablated expression of LFABP. Procedure: We obtained an LFABP knock-down model in Caco-2 cells by anti-mRNA overexpression. We analyzed the effect of this change in expression on the assimilation, metabolism and secretion of FA, as well as on the cellular proliferation and differentiation processes. Results: Several clones were isolated with less expression of LFABP compared to the control cells. No compensation by IFABP was observed in differentiated cells. Knock-down clones showed a marked decrease in oleate assimilation, while palmitate assimilation was increased. Differences in oleate distribution were observed at short times, but they disappeared after hours of incubation and no change in its distribution was observed in secreted lipids. On the other hand, cell proliferation and differentiation were slowed by the anti-sense clones compared to the control cells. Conclusions: Our results suggest that intestinal FABP would facilitate the intracellular transport of FA and that they could also have a role in the regulation of lipid metabolism and other cellular processes. The results presented indicate that LFABP is an important factor for the proper function of the enterocytes.