Am J Physiol Cell Physiol AJP: Regulatory, Integrative and Comparative Physiology
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Am J Physiol Cell Physiol 283: C688-C703, 2002. First published April 24, 2002; doi:10.1152/ajpcell.00586.2001
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Vol. 283, Issue 3, C688-C703, September 2002

Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L cell fibroblasts

Barbara P. Atshaves1, Stephen M. Storey1, Anca Petrescu1, Cynthia C. Greenberg1, Olga I. Lyuksyutova1, Roger Smith III2, and Friedhelm Schroeder1

Departments of 1 Physiology and Pharmacology and 2 Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, Texas 77843-4466

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, C16): 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 [3H]phytanic acid uptake (57-87%) and lipid accumulation (21-27%), nevertheless [3H]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 [3H]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.

sterol carrier protein-2; sterol carrier protein-x; liver fatty acid binding protein; fatty acids; phytanic acid; palmitic acid; lipid mass; toxicity


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