Clofibrate administration significantly altered the amount and fatty a
cid composition of lipids in mouse liver. The net content of phospholi
pids (PL) increased and that of triacylglycerols (TG) decreased concom
itantly 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 pho
sphatidylcholine; other components either showed lower increases or, a
s 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 20:3
n-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 c
hange affected all glycerolipid classes. Liver sphingomyelin showed a
relative enrichment in monoenoic fatty acids like 22:1 and 24:1, cause
d 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 grou
ps, either directly or after oxidation/desaturation processes. This wa
s apparently the case for the polyenoic fatty acids of the n-6 acid n-
3 series. The longer chain (C-22 and C-24) components decreased, sugge
sting that their oxidation was stimulated to provide part of the requi
red (C-20 and C-22) polyenes.