RESUMO
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.
Assuntos
Proteínas de Transporte/biossíntese , Fibroblastos/metabolismo , Metabolismo dos Lipídeos , Proteínas de Neoplasias , Proteínas do Tecido Nervoso , Ácido Palmítico/toxicidade , Ácido Fitânico/toxicidade , Proteínas de Plantas , Acetil-CoA C-Acetiltransferase/biossíntese , Acetil-CoA C-Acetiltransferase/genética , Animais , Western Blotting , Proteínas de Transporte/genética , Colesterol/metabolismo , Ésteres do Colesterol/metabolismo , Proteína 7 de Ligação a Ácidos Graxos , Proteínas de Ligação a Ácido Graxo , Ácidos Graxos não Esterificados/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Células L , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Oxirredução , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacocinética , Peroxissomos/metabolismo , Peroxissomos/ultraestrutura , Fosfolipídeos/metabolismo , Ácido Fitânico/metabolismo , Ácido Fitânico/farmacocinética , Soroalbumina Bovina/metabolismo , Soroalbumina Bovina/farmacologia , Frações Subcelulares/metabolismo , Frações Subcelulares/ultraestrutura , Transfecção , Triglicerídeos/metabolismo , TrítioRESUMO
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.
