Effect of Fatty Acid Saturation on the Distribution of the Cholesterol Moiety of Very Low Density Lipoproteins*

Abstract

The nonesterified cholesterol of each plasma lipoprotein fraction is in rapid exchange with that of red cells, liver, and other circulating lipoproteins (1-5). Although this dynamic equilibrium has been demonstrated in many species, including man, the factors determining the dynamics of this exchange and the resultant distribution of labeled cholesterol have not been elucidated. The present experiments, designed to test the possibility that the degree of saturation of the esterified fatty acids of lipoproteins could be such a factor, indicate that isotopic cholesterol associated with very low density lipoproteins composed largely of unsaturated fatty acids appears in other cholesterol pools more rapidly than that of saturated lipoproteins during both in vivo and in vitro equilibrations.traperitoneally in a small volume of 50% ethanol. The animals were exsanguinated 12 to 14 hours later and the very low density lipoproteins (< 1.019 fraction) harvested from their sera. This fraction from a safflowerfed animal was combined with one from an animal fed coconut oil and the mixture injected intravenously into a recipient rabbit. The fractions were selected so that in each study the cholesterol of one donor was labeled with C" and the other with tritium. The recipients were sacrificed 30 to 210 minutes after injection, and the ratio of the two isotopes was determined in the free and esterified fractions of their red cells, liver, whole serum, and < 1.019 and > 1.019 lipoprotein fractions. These isotope ratios were then compared to that injected. Changes in ratios were considered to indicate differences in dynamics of the cholesterol moiety of each type of lipoprotein. Each of these steps is discussed in more detail in the following paragraphs.

Effects of diet and high density lipoprotein subfractions on the removal of cellular cholesterol

“…To evaluate the possible effects of altered fatty acyl composition on the function of HDL, we have measured the removal of [3H]cholesterol from ascites cells using the HDL isolated during the various dietary periods. There were no differences The results of these experiments in man are different from those reported in the rabbit and pig (24,25). Spritz (24) and Yeh et al (25) found that the exchange of cholesterol from either very low density lipoproteins (VLDLs) or plasma was affected by the type of diet.…”

“…There were no differences The results of these experiments in man are different from those reported in the rabbit and pig (24,25). Spritz (24) and Yeh et al (25) found that the exchange of cholesterol from either very low density lipoproteins (VLDLs) or plasma was affected by the type of diet. Spritz (24) reported that VLDL isolated from rabbits fed safflower oil exchanged cholesterol significantly faster than cholesterol in VLDL from rabbits fed coconut oil.…”

Sterol Balance in Man as Plasma Cholesterol Concentrations Are Altered by Exchanges of Dietary Fats*

“…Most recently, Bieberdorf and Wilson (26) showed an increase in muscle cholesterol in the rabbit as plasma cholesterol concentrations decreased with the administration of an unsaturated oil. Spritz (30) has shown in rabbits that the fatty acid composition of lipoprotein fatty acids influences the transfer rate of isotopic cholesterol in a manner consistent with the concept that unsaturated dietary fat affects plasma cholesterol concentrations by altering equilibria between tissue and lipoprotein cholesterol pools. In contrast to these animal studies, however, Frantz and Carey (31) found no increase in liver cholesterol concentration in man as the plasma concentration was lowered by feeding unsaturated dietary fat.…”

The effects of unsaturated dietary fats on absorption, excretion, synthesis, and distribution of cholesterol in man

“…This conclusion has been supported by two lines of evidence developed by our colleagues Spritz and Mishkel. Spritz (39) has shown in rabbits that the fatty acid composition of the lipoproteins influences the rate of transfer of free cholesterol into tissues in a manner consistent with the concept that dietary unsaturated fats alter the equilibrium between tissue and lipoprotein pools of cholesterol. Later, Spritz and Mishkel (40) demonstrated in man that cholesterol-protein and phospholipid-to-protein ratios in low density lipoproteins fall during unsaturated fat feeding.…”