THE MECHANISM FOR THE INCREASED SUPPLY OF PHOSPHATIDYLCHOLINE FOR THE PROLIFERATION OF BIOLOGICAL-MEMBRANES BY CLOFIBRIC ACID, A PEROXISOME PROLIFERATOR

The metabolic changes induced by p-chlorophenoxyisobutyric acid (clofibric acid), a peroxisome proliferator, in hepatic glycerolipids for the supply of membrane phospholipids were studied. The administration of clofibric acid to rats caused hepatomegaly and an increase in hepatic contents of phosphatidylcholine (PtdCho) (1.13-fold on the basis of g liver and 1.50-fold on the basis of whole liver). The administration of the drug enhanced the formation in vivo of PtdCho from [H-3]glycerol, which seemed to be due to the increase in activity of CTP:phosphocholine cytidylyltransferase. On the other hand, clofibric acid depressed the activity of phosphatidylethanolamine N-methyltransferase. The in vivo study using [H-3]glycerol revealed that clofibric acid slightly reduced the secretion of PtdCho into circulation. On the other hand, the drug did not affect the turnover of PtdCho. These results may elucidate the metabolic alterations by which ciofibric acid increases hepatic mass of PtdCho. The facilitated biosynthesis of PtdCho by the drug seemed to lead to the increased formation of phosphatidylserine and subsequently phosphatidylethanolamine. Physiological significance of the alterations in glycerolipid metabolism by clofibric acid was discussed in relation to biological action of the drug.