Effects of clofibrate on lipids and fatty acids of mouse liver

Clofibrate administration significantly altered the amount and fatty acid composition of lipids in mouse liver. The net content of phospholipids (PL) increased and that of triacylglycerols (TG) decreased concomitantly with liver enlargement in mice treated for two weeks with this drug (0.5% w/w in the food). The highest increase among PL was in phosphatidylcholine; other components either showed lower increases or, as in the case of sphingomyelin and the plasmalogens, decreased. In all lipid classes the treatment resulted in altered ratios between major saturates, between saturates and monoenes, and between major polyenes. Among these, 20:3n-6 and 22:5n-3 increased several-fold, and the 20:3n-6/20:4n-6 and 22:5n-3/22:6n-3 ratios increased due to a more active formation of the precursors than of the corresponding products. This change affected all glycerolipid classes. Liver sphingomyelin showed a relative enrichment in monoenoic fatty acids like 22:1 and 24:1, caused by a net decrease in the amount of saturates, particularly 22:0 and 24:0. The stimulated membrane proliferation imposed by clofibrate must increase phospholipid synthesis and, hence, the need for fatty acids. The results suggest that these demands are met mostly by TG acyl groups, either directly or after oxidation/desaturation processes. This was apparently the case for the polyenoic fatty acids of the n-6 and n-3 series. The longer chain (C22 and C24) components decreased, suggesting that their oxidation was stimulated to provide part of the required (C20 and C22) polyenes.