Effects of the unsaturation of dietary fat and of arachidonate supplementation on cholesterol pool expansion in the guinea pigs.

We have studied the effects of methyl arachidonate supplementation on the lipid metabolism of guinea pigs fed cholesterol. Four groups of guinea pigs were fed a purified diet containing 9.5% hydrogenated coconut oil (HCNO), a highly saturated fat with or without the addition of 1% cholesterol, for 15 weeks. One half of the animals fed the control and the cholesterol-containing diets were supplemented with 15 mg methyl arachidonate three times per week. Supplementation with methyl arachidonate did not alter the concentration of plasma total (TC) or unesterified (FC) cholesterol, erythrocyte cholesterol and plasma phospholipid or the ratio of plasma FC/TC. Accumulation of cholesterol in the major organs of the cholesterol-fed groups was also unchanged. In both control and cholesterol-fed groups, methyl arachidonate decreased the proportion of oleic (18:1) and linoleic acids (18:2) and increased arachidonic acid (20:4) content of plasma and liver phospholipid. A comparison between the results of this study and studies using cottonseed oil showed that the type of dietary fat modifies the effects of cholesterol: plasma cholesterol levels were higher and liver cholesterol storage was lower in animals fed the saturated fat than in those fed the fat rich in polyunsaturated fatty acids (PUFA). Furthermore, in spite of similar changes in erythrocyte cholesterol content and shape abnormalities, no overt hemolytic anemia was observed in the groups fed cholesterol and saturated fat, in contrast to those fed cholesterol + PUFA-containing fat. We conclude that in guinea pigs supplementary methyl arachidonate had no hypocholesterolemic effect at the levels we fed, that circulating cholesterol levels are not a measure of cholesterol accumulation by organs and that the decrease of serum cholesterol in response of PUFA is due in part to an increase of cholesterol storage in the liver.