Decreased liver fatty acid binding capacity and altered liver lipid distribution in mice lacking the liver fatty acid-binding protein gene

Item Type:	Article
Title:	Decreased liver fatty acid binding capacity and altered liver lipid distribution in mice lacking the liver fatty acid-binding protein gene
Creators Name:	Martin, G.G. and Danneberg, H. and Kumar, L.S. and Atshaves, B.P. and Erol, E. and Bader, M. and Schroeder, F. and Binas, B.
Abstract:	Although liver fatty acid-binding protein (L-FABP) is an important binding site for various hydrophobic ligands in hepatocytes, its in vivo significance is not understood. We have therefore created L-FABP null mice and report here their initial analysis, focusing on the impact of this mutation on hepatic fatty acid binding capacity, lipid composition, and expression of other lipid-binding proteins. Gel-filtered cytosol from L-FABP null liver lacked the main fatty acid binding peak in the fraction that normally comprises both L-FABP and sterol carrier protein-2 (SCP-2). The binding capacity for cis-parinaric acid was decreased > 80% in this region. Molar ratios of cholesterol/cholesterol ester, cholesteryl ester/triglyceride, and cholesterol/phospholipid were 2-to 3-fold greater, reflecting up to 3-fold absolute increases in specific lipid classes in the order cholesterol > cholesterol esters > phospholipids. In contrast, the liver pool sizes of nonesterified fatty acids and triglycerides were not altered. However, hepatic deposition of a bolus of intravenously injected [ 14C]oleate was markedly reduced, showing altered lipid pool turnover. An increase of ∼75% of soluble SCP-2 but little or no change of other soluble (glutathione S-transferase, albumin) and membrane (fatty acid transport protein, CD36, aspartate aminotransferase, caveolin) fatty acid transporters was measured. These results (i) provide for the first time a quantitative assessment of the contribution of L-FABP to cytosolic fatty acid binding capacity, (ii) establish L-FABP as an important determinant of hepatic lipid composition and turnover, and (iii) suggest that SCP-2 contributes to the accumulation of cholesterol in L-FABP null liver.
Keywords:	Acetyl-CoA C-Acetyltransferase, Carrier Proteins, Cell Membrane, Cholesterol, Cholesterol Esters, Complementary DNA, Cytosol, Drug Dose-Response Relationship, Fatty Acid-Binding Proteins, Fatty Acids, Gel Chromatography, Genetic Models, Glutathione Transferase, Kinetics, Ligands, Lipid Metabolism, Liver, Mutation, Neoplasm Proteins, Nerve Tissue Proteins, Polyacrylamide Gel Electrophoresis, Phospholipids, Protein Binding, Recombinant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Subcellular Fractions, Transgenic Mice, Triglycerides, Unsaturated Fatty Acids, Western Blotting, Animals, Mice, Rats
Source:	Journal of Biological Chemistry
ISSN:	0021-9258
Publisher:	American Society for Biochemistry and Molecular Biology
Volume:	278
Number:	24
Page Range:	21429-21438
Date:	1 January 2003
Official Publication:	https://doi.org/10.1074/jbc.M300287200
PubMed:	View item in PubMed

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