Submitted on August 14, 2007
Revised on January 11, 2008
Accepted on January 30, 2008
Intestinal fatty acid binding protein regulates mitochondrion 
-oxidation and cholesterol uptake
Alain Montoudis, Ernest Seidman, François Boudreau, Jean François Beaulieu, Daniel Ménard, Mounib ElChebly, Geneviève Mailhot, Alain-Theophile Sané, Marie Lambert, Edgard Delvin, and Emile Levy
Nutrition, Hôpital Ste-Justine, Montréal, Québec H3T 1C5
Corresponding Author: emile.levy{at}recherche-ste-justine.qc.ca
The role of I-FABP in lipid metabolism remains elusive. To address this issue, HIEC-6 cells were transfected with cDNA to overexpress I-FABP and compared with cells treated with empty pQCXIP vector. I-FABP overexpression (~90-fold) stimulated mitochondrial [U-14C]-oleate oxidation to CO2 and acid-soluble metabolites via mechanisms that include: (i) up-regulation of the protein expression and activity of CPT1, a critical enzyme that controls entry of fatty acids (FA) into mitochondria and, thereby, their oxidation; (ii) increased activity of L3HOAD, a mitochondrial 
-oxidation enzyme. On the other hand, the gene and protein expression of the key enzymes FA synthase and ACC2 was decreased, suggesting diminished lipogenesis. Furthermore, I-FABP overexpression caused a decline in the ability of HIEC-6 to incorporate micellar [14C-free cholesterol. Accordingly, a significant lessening was observed in the gene expression of NPC1L1, a mediator of cholesterol (CHOL) uptake, along with a rise in the transcripts and protein content of ABCA1 and ABCG5/ABCG8 acting as CHOL efflux pumps. Furthermore, I-FABP overexpression resulted in increased levels of mRNA, protein mass and activity of HMG-CoA reductase, the rate-limiting step in CHOL synthesis, without any change in ACAT2, the key enzyme in CHOL esterification. Scrutiny of the nuclear receptors revealed augmented PPAR
and PPAR
, reduced LXR and unaltered RXR and SREBP2 in HIEC-6 overexpressing I-FABP. Finally, I-FABP overexpression did not influence the ACOX1 that catalyzes the first rate-limiting step in peroxisomal FA -oxidation. Overall, our data suggest that I-FABP may influence mitochondrial FA oxidation and CHOL transport by regulating gene expression and interaction with nuclear receptors.
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