Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L cell fibroblasts.
High levels of saturated, branched-chain fatty acids are deleterious to cells and animals, resulting in lipid accumulation and cytotoxicity. Although fatty acid binding proteins (FABPs) are thought to be protective, this hypothesis has not previously been examined. Phytanic acid (branched chain, 16-carbon backbone) induced lipid accumulation in L cell fibroblasts similar to that observed with palmitic acid (unbranched, C(16)): triacylglycerol >> free fatty acid > cholesterol > cholesteryl ester >> phospholipid. Although expression of sterol carrier protein (SCP)-2, SCP-x, or liver FABP (L-FABP) in transfected L cells reduced [(3)H]phytanic acid uptake (57-87%) and lipid accumulation (21-27%), nevertheless [(3)H]phytanic acid oxidation was inhibited (74-100%) and phytanic acid toxicity was enhanced in the order L-FABP >> SCP-x > SCP-2. These effects differed markedly from those of [(3)H]palmitic acid, whose uptake, oxidation, and induction of lipid accumulation were not reduced by L-FABP, SCP-2, or SCP-x expression. Furthermore, these proteins did not enhance the cytotoxicity of palmitic acid. In summary, intracellular FABPs reduce lipid accumulation induced by high levels of branched-chain but not straight-chain saturated fatty acids. These beneficial effects were offset by inhibition of branched-chain fatty acid oxidation that correlated with the enhanced toxicity of high levels of branched-chain fatty acid.
Atshaves
Barbara P
BP
Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station 77843-4466, USA.
Storey
Stephen M
SM
Petrescu
Anca
A
Greenberg
Cynthia C
CC
Lyuksyutova
Olga I
OI
Smith
Roger
R
Schroeder
Friedhelm
F
D000101:Acetyl-CoA C-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007739:L Cells; D050356:Lipid Metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D020675:Peroxisomes / Q000378:metabolism / Q000648:ultrastructure; D010743:Phospholipids / Q000378:metabolism; D010831:Phytanic Acid / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D010940:Plant Proteins; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D014316:Tritium
D002352:Carrier Proteins; D002788:Cholesterol Esters; C493320:Fabp1 protein, mouse; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010743:Phospholipids; D010940:Plant Proteins; D014280:Triglycerides; C072087:sterol carrier proteins; D014316:Tritium; D010831:Phytanic Acid; D012710:Serum Albumin, Bovine; D019308:Palmitic Acid; D002784:Cholesterol; D000101:Acetyl-CoA C-Acetyltransferase