Ablation of the Liver Fatty Acid Binding Protein Gene Decreases Fatty Acyl CoA Binding Capacity and Alters Fatty Acyl CoA Pool Distribution in Mouse Liver
- 10 September 2003
- journal article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 42 (39), 11520-11532
- https://doi.org/10.1021/bi0346749
Abstract
Although liver fatty acid binding protein (L-FABP) is known to bind not only long chain fatty acid (LCFA) but also long chain fatty acyl CoA (LCFA-CoA), the physiological significance of LCFA-CoA binding has been questioned and remains to be resolved. To address this issue, the effect of L-FABP gene ablation on liver cytosolic LCFA-CoA binding, LCFA-CoA pool size, LCFA-CoA esterification, and potential compensation by other intracellular LCFA-CoA binding proteins was examined. L-FABP gene ablation resulted not only in loss of L-FABP but also in concomitant upregulation of two other intracellular LCFA-CoA binding proteins, acyl CoA binding protein (ACBP) and sterol carrier protein-2 (SCP-2), by 45 and 80%, respectively. Nevertheless, the soluble fraction from livers of L-FABP (−/−) mice bound 95% less radioactive oleoyl-CoA than wild-type L-FABP (+/+) mice. The intracellular LCFA-CoA binding protein fraction (Fraction III) from wild-type L-FABP (+/+) mice, isolated by gel permeation chromatography of liver soluble proteins, exhibited one high-affinity binding and several low-affinity binding sites for cis-parinaroyl-CoA, a naturally occurring fluorescent LCFA-CoA. In contrast, high-affinity LCFA-CoA binding was absent from Fraction III of L-FABP (−/−) mice. While L-FABP gene ablation did not alter liver LCFA-CoA pool size, LCFA-CoA acyl chains of L-FABP (−/−) mouse livers were enriched 2.1-fold in C16:1 and decreased 1.9-fold in C20:0 fatty acids. Finally, L-FABP gene ablation selectively increased the amount of LCFAs esterified into liver phospholipid > cholesteryl ester, while concomitantly decreasing the amount of fatty acids esterified into triglycerides by 40%. In summary, these data with L-FABP (−/−) mice demonstrated for the first time that L-FABP is a physiologically significant contributor to determining liver cytosolic LCFA-CoA binding capacity, LCFA-CoA acyl chain distribution, and esterified fatty acid distribution.Keywords
This publication has 21 references indexed in Scilit:
- Rescue of MODY-1 by Agonist Ligands of Hepatocyte Nuclear Factor-4αPublished by Elsevier BV ,2003
- Ligand Specificity and Conformational Dependence of the Hepatic Nuclear Factor-4α (HNF-4α)Published by Elsevier BV ,2002
- Acyl-CoA Esters Antagonize the Effects of Ligands on Peroxisome Proliferator-activated Receptor α Conformation, DNA Binding, and Interaction with Co-factorsPublished by Elsevier BV ,2001
- Sterol carrier protein-2 localization in endoplasmic reticulum and role in phospholipid formationAmerican Journal of Physiology-Cell Physiology, 2000
- Role of acylCoA binding protein in acylCoA transport, metabolism and cell signalingMolecular and Cellular Biochemistry, 1999
- Fatty acid binding protein isoforms: structure and functionChemistry and Physics of Lipids, 1998
- Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signallingBiochemical Journal, 1997
- Acyl-CoA-binding protein (ACBP) can mediate intermembrane acyl-CoA transport and donate acyl-CoA for β-oxidation and glycerolipid synthesisBiochemical Journal, 1994
- Expression of rat L-FABP in mouse fibroblasts: role in fat absorptionMolecular and Cellular Biochemistry, 1993
- Na pump and plasma membrane structure in L-cell fibroblasts expressing rat liver fatty acid binding proteinArchives of Biochemistry and Biophysics, 1992