期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 283, 期 3, 页码 C688-C703出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00586.2001
关键词
sterol carrier protein-2; sterol carrier protein-x; liver fatty acid binding protein; fatty acids; phytanic acid; palmitic acid; lipid mass; toxicity
资金
- NIDDK NIH HHS [DK-41402] Funding Source: Medline
- NIGMS NIH HHS [GM-31651] Funding Source: Medline
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 [H-3] phytanic acid uptake (57-87%) and lipid accumulation (21-27%), nevertheless [H-3] 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 [H-3] 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.
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