Dynamics of Apolipoprotein E Metabolism in Humans

The dynamics of human apoE metabolism were explored by examining the effects of alimentary lipemia and postheparin lipolysis on the plasma level and lipoprotein distribution of apoE. In the studies of alimentary lipemia, fasting and postprandial plasma samples were obtained from five normal adult males, each of whom drank 100 g of corn oil. Although no change in the plasma concentration of apoE accompanied alimentary lipemia, a major redistribution of apoE among lipoproteins occurred. The portion of apoE associated with triglyceride-rich lipoproteins as assessed by agarose column chromatography increased by a mean of 44%. Furthermore, in the two subjects in whom multiple postprandial samples were taken, there were striking linear correlations between plasma triglyceride concentrations and the fraction of apoE in triglyceride-rich lipoproteins (r = 0.96 and 0.73). In contrast, the plasma concentration of apoE fell in each of the seven studies of postheparin lipolysis. The fall averaged 17% of the control plasma apoE level. In hypertriglyceridemic patients, the decline in plasma triglyceride concentration preceded the decline in apoE concentration, suggesting that the decline in apoE was due to removal of remnants of triglyceride-rich lipoproteins. Lipoprotein fractionation demonstrated substantial loss of apoE from triglyceride-rich lipoproteins; the data suggested that this loss of apoE from triglyceride-rich lipoproteins was due both to removal of apoE from plasma and to transfer of apoE to an HDL fraction. During the recovery phase, as plasma triglyceride levels rose, opposite changes occurred: the plasma apoE level rose, apoE in triglyceride-rich lipoproteins increased in concentration, and apoE in HDL decreased in concentration. Furthermore, it became apparent during the recovery phase that apoE in triglyceride-rich lipoproteins was composed of two discrete subfractions. The first subfraction consisted of apoE on larger, probably recently synthesized lipoproteins; the second consisted of apoE on much smaller lipoproteins. These studies provide evidence in intact humans for a dynamic traffic of apoE between triglyceride-rich lipoproteins and high density lipoprotein. This traffic is a prominent phenomenon of normal alimentary lipemia and of lipolysis. By modulating the lipoprotein distribution of apoE, it probably plays a key functional role in lipoprotein metabolism.-Blum, C. B. Dynamics of apolipoprotein E metabolism in humans.