Effects of intestinal fatty acid-binding protein overexpression on fatty acid metabolism in Caco-2 cells

Intestinal fatty acid-binding protein (I-FABP) is a cytosolic protein expre ssed at high levels (up to 270 of cytosolic proteins) in the small intestin e epithelium, Despite cell transfection studies, its function is still uncl ear, Indeed, different effects on fatty acid metabolism depending on the ce ll type and the amount of I-FABP expressed have been reported, Furthermore, a decrease in fatty acid incorporation has been unexpectedly obtained when I-FABP reached 0.72% of cytosolic proteins in fibroblasts (Prows et al. 19 97, Arch. Biochem. Biophys. 340: 135), In the present study, the effect of a high level of I-FABP similar to amounts present in the small intestine wa s investigated in the human colon adenocarcinoma cell Line, Caco-2, After t ransfection with human I-FABP cDNA, a clone expressing 1.5% I-FABP and unch anged level of Liver FABP was selected. These cells, which had a lower I at e of proliferation as compared with mock-transfected cells, developed the t ypical morphological characteristics of differentiated enterocyte, Incubati on of differentiated cells with [C-14]palmitate shelved a 34% reduction (P < 0.01) of fatty acid incorporation, whereas the relative distribution of r adiolabel into triglycerides was not affected, A nonsignificant 21% reducti on of fatty acid incorporation was observed with another clone expressing 1 0-fold less I-FABP. In conclusion, a high level of I-FABP expressed in a di fferentiated enterocyte model inhibited fatty acid incorporation, by a mech anism which remains to be defined.