title: Liver fatty acid-binding protein gene ablation inhibits branched-chain fatty acid metabolism in cultured primary hepatocytes.
abstract: Whereas the role of liver fatty acid-binding protein (L-FABP) in the uptake, transport, mitochondrial oxidation, and esterification of normal straight-chain fatty acids has been studied extensively, almost nothing is known regarding the function of L-FABP in peroxisomal oxidation and metabolism of branched-chain fatty acids. Therefore, phytanic acid (most common dietary branched-chain fatty acid) was chosen to address these issues in cultured primary hepatocytes isolated from livers of L-FABP gene-ablated (-/-) and wild type (+/+) mice. These studies provided three new insights: First, L-FABP gene ablation reduced maximal, but not initial, uptake of phytanic acid 3.2-fold. Initial uptake of phytanic acid uptake was unaltered apparently due to concomitant 5.3-, 1.6-, and 1.4-fold up-regulation of plasma membrane fatty acid transporter/translocase proteins (glutamic-oxaloacetic transaminase, fatty acid transport protein, and fatty acid translocase, respectively). Second, L-FABP gene ablation inhibited phytanic acid peroxisomal oxidation and microsomal esterification. These effects were consistent with reduced cytoplasmic fatty acid transport as evidenced by multiphoton fluorescence photobleaching recovery, where L-FABP gene ablation reduced the cytoplasmic, but not membrane, diffusional component of NBD-stearic acid movement 2-fold. Third, lipid analysis of the L-FABP gene-ablated hepatocytes revealed an altered fatty acid phenotype. Free fatty acid and triglyceride levels were decreased 1.9- and 1.6-fold, respectively. In summary, results with cultured primary hepatocytes isolated from L-FABP (+/+) and L-FABP (-/-) mice demonstrated for the first time a physiological role of L-FABP in the uptake and metabolism of branched-chain fatty acids.
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, Texas 77843-4466, USA.
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Atshaves
authors.forename: Avery M
authors.initials: AM
authors.lastname: McIntosh
authors.forename: Olga I
authors.initials: OI
authors.lastname: Lyuksyutova
authors.forename: Warren
authors.initials: W
authors.lastname: Zipfel
authors.forename: Watt W
authors.initials: WW
authors.lastname: Webb
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D018390:Gene Targeting; D022781:Hepatocytes / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010084:Oxidation-Reduction
chemical_list: D002352:Carrier Proteins; C493320:Fabp1 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids