Intestinal fatty acid binding protein regulates mitochondrion β-oxidation and cholesterol uptake

• Published in: Journal of lipid research Vol. 49; no. 5; pp. 961 - 972
• Main Authors: Montoudis, Alain, Seidman, Ernest, Boudreau, François, Beaulieu, Jean-François, Menard, Daniel, Elchebly, Mounib, Mailhot, Geneviève, Sane, Alain-Theophile, Lambert, Marie, Delvin, Edgard, Levy, Emile
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2008; American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; Base Sequence; Cell Line; Cholesterol - metabolism; DNA Primers; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - physiology; HIEC-6; Homeostasis; Humans; Hydroxymethylglutaryl CoA Reductases - metabolism; I-FABP; Intestinal Mucosa - metabolism; Mitochondria - metabolism; Molecular Sequence Data; Oleic Acid - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Transfection; I-FABP; HIEC-6; cholesterol metabolism
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M700363-JLR200

The role of intestinal fatty acid binding protein (I-FABP) in lipid metabolism remains elusive. To address this issue, normal human intestinal epithelial cells (HIEC-6) were transfected with cDNA to overexpress I-FABP and compared with cells treated with empty pQCXIP vector. I-FABP overexpression stimulated mitochondrial [U-14C]oleate oxidation to CO2 and acid-soluble metabolites via mechanisms including the upregulation of protein expression and the activity of carnitine palmitoyltransferase 1, a critical enzyme controlling the entry of fatty acid (FA) into mitochondria, and increased activity of 3-hydroxyacyl-CoA dehydrogenase, a mitochondrial β-oxidation enzyme. On the other hand, the gene and protein expression of the key enzymes FA synthase and acetyl-coenzyme A carboxylase 2 was decreased, suggesting diminished lipogenesis. Furthermore, I-FABP overexpression caused a decline in [14C]free cholesterol (CHOL) incorporation. Accordingly, a significant lessening was observed in the gene expression of Niemann Pick C1-Like 1, a mediator of CHOL uptake, along with an increase 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. Scrutiny of the nuclear receptors revealed augmented peroxisome proliferator-activated receptor α,γ and reduced liver X receptor-α in HIEC-6 overexpressing I-FABP. Finally, I-FABP overexpression did not influence acyl-coenzyme A oxidase 1, which catalyzes the first rate-limiting step in peroxisomal FA β-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.