ABSTRACT
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.
Subject(s)
Carrier Proteins/biosynthesis , Fibroblasts/metabolism , Lipid Metabolism , Neoplasm Proteins , Nerve Tissue Proteins , Palmitic Acid/toxicity , Phytanic Acid/toxicity , Plant Proteins , Acetyl-CoA C-Acetyltransferase/biosynthesis , Acetyl-CoA C-Acetyltransferase/genetics , Animals , Blotting, Western , Carrier Proteins/genetics , Cholesterol/metabolism , Cholesterol Esters/metabolism , Fatty Acid-Binding Protein 7 , Fatty Acid-Binding Proteins , Fatty Acids, Nonesterified/metabolism , Fibroblasts/cytology , Fibroblasts/drug effects , L Cells , Mice , Mitochondria/metabolism , Mitochondria/ultrastructure , Oxidation-Reduction , Palmitic Acid/metabolism , Palmitic Acid/pharmacokinetics , Peroxisomes/metabolism , Peroxisomes/ultrastructure , Phospholipids/metabolism , Phytanic Acid/metabolism , Phytanic Acid/pharmacokinetics , Serum Albumin, Bovine/metabolism , Serum Albumin, Bovine/pharmacology , Subcellular Fractions/metabolism , Subcellular Fractions/ultrastructure , Transfection , Triglycerides/metabolism , TritiumABSTRACT
Five patients with Refsum's disease were treated by plasma exchange. Lowering the plasma phytanic acid by plasma exchange in patients acutely ill with Refsum's disease produced clinical improvement. Plasma exchange is indicated in Refsum's disease when there is a worsening clinical condition. Occasionally, failure of dietary control of Refsum's disease may necessitate plasma exchange.
