Metabolic alterations by clofibric acid in the formation of molecular species of phosphatidylcholine in rat liver

The mechanism by which p-chlorophenoxyisobutyric acid (clofibric acid) indu ces striking changes in the proportion of the molecular species of phosphat idylcholine (PC) in rat liver was studied. Treatment of rats with clofibric acid strikingly increased the content of 1-palmitoyl-2-oleoyl (16:0-18:1) PC, but decreased the contents of 1-palmitoyl-2-docosahexaenoyl (16:0-22:6) , 1-stearoyl-2-arachidonoyl (18:0-20:4), and 1-stearoyl-2-linoleoyl (18:0-1 8:2) PC; the drug did not change the content of 1-almitoyl-2-arachidonoyl ( 16:0-20:4) PC. The mechanism underlying these changes has been investigated with regard to the in vivo formation of the molecular species of PC by: (i ) de novo synthesis, (ii) reacylation, and (iii) methylation of phosphatidy lethanolamine (PE). We found that (i) the incorporation of [H-3]glycerol, w hich was injected intravenously, into 16:0-18:1 diacylglycerol (DG) and 16: 0-18:1 PC was increased markedly by clofibric acid feeding without changing the substrate specificity of CDP-choline:DG cholinephosphotransferase, (ii ) the in vivo formation of 16:0-18:1 and 16:0-20:4 PC from 1-16:0-[H-3]glyc erophosphocholine (GPC), which was injected intraportally, was increased ma rkedly by clofibric acid feeding, and (iii) the incorporation of [C-14]etha nolamine, which was injected intravenously into 16:0-22:6, 18:0-22:6, and 1 8:0-20:4 PC, was decreased by clofibric acid feeding; the extent of the dec rease in 16:0-20:4 PC was less than that of 18:0-20:4 PC. It was concluded, therefore, that (i) clofibric acid selectively increased the content and p roportion of 16:0-18:1 PC by enhancing both the CDP-choline pathway and the remodeling of the pre-existing PC molecule, and (ii) the drug kept the con tent of 16:0-20:4 PC unchanged by stimulating the remodeling of the pre-exi sting PC molecule, whereas the formation of other more long chain, polyunsa turated molecular species, such as 16:0-22:6, 18:0-22:6, and 18:0-20:4, was decreased owing to the suppression of PE methylation. (C) 2001 Elsevier Sc ience Inc. All rights reserved.