ANALYSIS OF THE SPECIFIC ROLES OF THE ENTEROCYTE FATTY ACID BINDING PROTEINS (FABP): INTESTINAL AND LIVER- FABP.

RODRIGUEZ SAWICKI LUCIANA; BOTTASSO ARIAS NATALIA; GARCIA KARINA ALEJANDRA; FALOMIR LOCKHART LISANDRO JORGE; FRANCHINI GISELA RAQUEL; STORCH JUDITH; SCAGLIA NATALIA; CÓRSICO BETINA

Puerto Iguazu

Congreso; 56th International Conference on the Bioscience of lipids; 2015

Lipid hydrolysis in the intestinal lumen releases great quantities of long chain fatty acids (LCFA). Following uptake, they are reversibly bound to two proteins that are abundantly expressed in the enterocytes: intestinal (I-) and liver (L-) FABP. Their different tissue distribution and binding properties suggest that they have non-redundant functions within the enterocyte. To study intestinal FABPs functions, we generated a LFABP knockdown model in Caco-2 cell line by an mRNA antisense strategy. Clonal and no-clonal stable knockdown populations were selected and control cells were transfected with an empty vector. LFABP expression was reduced up to 85% in different populations and no compensatory increase in IFABP was observed, strengthening the idea of differential functions of both isoforms. LFABP reduction decreased cell proliferation and slightly slowed differentiation. The role of LFABP on membrane phospholipid synthesis, β-oxidation and regulation of gene expression is currently under study. LFABP knockdown cells showed a marked decrease in oleate assimilation from the apical side and differences in its distribution within lipid species at short times. LFABP depletion reduced basolateral oleate secretion as well. The secreted oleate distribution showed an increase in fatty acid/triacylglyceride ratio compared to control cells, probably due to LFABP?s role in chylomicron assembly. Thus, these results suggest that LFABP is involved both in apical FA uptake and their intracellular metabolism for basolateral secretion. Overall, our study indicates that LFABP is essential for the proper function of the enterocytes, even in the presence of physiological concentrations of IFABP.