PMID:18235139
| Citation |
Montoudis, A, Seidman, E, Boudreau, F, Beaulieu, JF, Menard, D, Elchebly, M, Mailhot, G, Sane, AT, Lambert, M, Delvin, E and Levy, E (2008) Intestinal fatty acid binding protein regulates mitochondrion beta-oxidation and cholesterol uptake. J. Lipid Res. 49:961-72 |
|---|---|
| Abstract |
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 beta-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 alpha,gamma and reduced liver X receptor-alpha 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 beta-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. |
| Links |
PubMed Online version:10.1194/jlr.M700363-JLR200 |
| Keywords |
ATP-Binding Cassette Transporters/genetics; Base Sequence; Cell Line; Cholesterol/metabolism; DNA Primers; Fatty Acid-Binding Proteins/genetics; Fatty Acid-Binding Proteins/physiology; Homeostasis; Humans; Hydroxymethylglutaryl CoA Reductases/metabolism; Intestinal Mucosa/metabolism; Mitochondria/metabolism; Molecular Sequence Data; Oleic Acid/metabolism; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction; Transfection |
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