Essential fatty acid deficiency and cholesterol esterification activity of plasma and liver in vitro and in vivo

The esterification of cholesterol in vitro and in vivo was studied in rats fed diets containing and deficient in essential fatty acids (EFA). EFA deficiency resulted in increased cholesterol esterification activity in vitro, and this appeared to reflect an increased plasma cholesterol esterification activity in vitro, and this appeared to reflect an increase in enzyme concentrations. There was a decrease in plasma lipid phosphorus concentrations during the period of cholesterol esterification. Certain aspect of the fatty acid compositions of plasma phospholipids and cholesterol esters were consistent with a role of phospholipid fatty acids in the transesterification reaction which has been demonstrated by Glomset et al. (18). There was heterogeneous labeling of different subclasses of cholesterol esters when cholesterol-4-C¹⁴ was used as the substrate, the more unsaturated fatty acid esters having the highest relative specific activities. EFA deficiency resulted in decreased cholesterol esterification activity by hepatocytic organelles. This activity was also reduced when organelles were exposed to hypotonic media, ultrasound, or taurocholate. Rats deficient in EFA had increased rates of esterification of cholesterol-4-C¹⁴ in plasma and increased rates of elimination of radiocholesterol from the plsama after intravenous injection of labeled lipoproteins. This was associated with higher concentrations of total radioactivity in the livers of the EFA deficient rats. The specific activities of individual subclasses of cholesterol esters of plasma and liver were also heterogeneous for several hours in these in vivo experiments regardless of the dietary regimen involved. The more unsaturated fatty acid esters had the highest initial specific activities. Although liver and plasma free cholesterol specific activities rapidly equilibrated, the specific activities of the cholesterol esters and individual subclasses of cholesterol esters of plasma were greater than the activities of corresponding fractions from liver. It was proposed that the differences in plasma and liver esterification activities induced by EFA deficiency were secondary to alterations in the stability of hepatocytic organelles.