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Articles in PresS, published online ahead of print April 24, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00586.2001
Submitted on December 10, 2001
Accepted on April 18, 2002
1 Physiology&Pharmacology TVMC, Texas A&M University, College Station, TX, USA
2 Pathobiology TVMC, Texas A&M University, College Station, TX, USA
* To whom correspondence should be addressed. E-mail: fschroeder{at}cvm.tamu.edu.
High levels of saturated, especially branched-chain, fatty acids are deleterious to cultured cells and animals resulting in lipid accumulation and cytotoxicity. Although intracellular fatty acid binding proteins are thought to be protective, this hypothesis has not previously been examined. Phytanic acid (C-16 chain-length, 4 methyl-branched) induced lipid accumulation in L-cell fibroblasts similar to that observed with palmitic acid (C16 chain-length, unbranched): triacylglycerol >> free fatty acid > cholesterol > cholesteryl ester >> phospholipid. While expression of sterol carrier protein-2 (SCP-2), sterol carrier protein-x (SCP-x), or liver fatty acid binding protein (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 were specific and differed markedly from those of [3H]palmitic acid whose uptake, oxidation, or induction of lipid accumulation were not (or only slightly) reduced by L-FABP, SCP-2, or SCP-x expression. Furthermore, these proteins did not enhance the cytotoxicity of palmitic acid. In summary, the data support the hypothesis that intracellular fatty acid binding proteins (L-FABP, SCP-2, and SCP-x) reduce lipid accumulation induced by high levels of branched-, but not straight-, chain saturated fatty acid. However, these beneficial effects were offset by inhibition of branched-chain fatty acid oxidation which correlated with the enhanced toxicity of high levels of branched chain fatty acid.
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