Liver fatty acid binding protein expression enhances branched-chain fatty acid metabolism
- 135 Downloads
Although liver fatty acid binding protein (L-FABP) is known to enhance uptake and esterification of straight-chain fatty acids such as palmitic acid and oleic acid, its effects on oxidation and further metabolism of branched-chain fatty acids such as phytanic acid are not completely understood. The present data demonstrate for the first time that expression of L-FABP enhanced initial rate and average maximal oxidation of [2,3−3H] phytanic acid 3.5− and 1.5−fold, respectively. This enhancement was not due to increased [2,3−3H] phytanic acid uptake, which was only slightly stimulated (20%) in L-FABP expressing cells after 30 min. Similarly, L-FABP also enhanced the average maximal oxidation of [9,10−3H] palmitic acid 2.2−fold after incubation for 30 min. However, the stimulation of L-FABP on palmitic acid oxidation nearly paralleled its 3.3−fold enhancement of uptake. To determine effects of metabolism on fatty acid uptake, a non-metabolizable fluorescent saturated fatty acid, BODIPY-C16, was examined by laser scanning confocal microscopy (LSCM). L-FABP expression enhanced uptake of BODIPY-C16 1.7−fold demonstrating that L-FABP enhanced saturated fatty acid uptake independent of metabolism. Finally, L-FABP expression did not significantly alter [2,3−3H] phytanic acid esterification, but increased [9,10−3H] palmitic acid esterification 4.5−fold, primarily into phospholipids (3.7−fold) and neutral lipids (9−fold). In summary, L-FABP expression enhanced branched-chain phytanic acid oxidation much more than either its uptake or esterification. These data demonstrate a potential role for L-FABP in the peroxisomal oxidation of branched-chain fatty acids in intact cells.
Unable to display preview. Download preview PDF.
- 4.Starodub OT: Intracellular localization and functional implications of sterol carrier protein-2 (SCP-2) gene products and liver fatty acid binding protein (L-FABP) in transfected L-cell fibroblasts. Texas A&M University, College Station, TX 77843-4466, 2002Google Scholar
- 8.Murphy EJ: L-FABP and I-FABP expression increase NBD-stearate uptake and cytoplasmic diffusion in L-cells. Am J Physiol 38: G244-G249, 1998Google Scholar
- 10.Weisiger RA: Cytoplasmic transport of lipids: Role of binding proteins. Comp Biochem Physiol 115B: 319-331, 1996Google Scholar
- 11.Weisiger RA: When is a carrier not a membrane carrier? The cytoplasmic transfer of amphipathic molecules. Hepatology 24: 1288-1295, 1998Google Scholar
- 17.Steinberg D: In: C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle (eds), The Metabolic Basis of Inherited Disease. McGraw-Hill, New York, 1990, pp 1533-1550Google Scholar
- 18.Avigan J: The presence of phytanic acid in normal human and animal plasma. Biochim Biophys Acta 166: 391-394, 1966Google Scholar
- 26.Atshaves BP, Storey SM, Petrescu AD, Greenberg CC, Lyuksyutova OI, Smith R, Schroeder F: Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L-cell fibroblasts. Am J Physiol 283: C688-C703, 2002Google Scholar
- 27.Seedorf U, Raabe M, Ellinghaus P, Kannenberg F, Fobker M, Engel T, Denis S, Wouters F, Wirtz KWA, Wanders RJA, Macda N, Assmann G: Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes Dev 12: 1189-1201, 1998PubMedGoogle Scholar
- 41.Moser HW, Moser AB: Peroxisomal disorders: Overview. In: J.K. Reddy, T. Suga, G.P. Mannaerts, P.B. Lazarow, S. Subramani (eds). Peroxisomes: Biology and Role in Toxicology and Disease. Ann NY Acad Sci, New York, 1996, pp 427-441Google Scholar