HEPATIC-CLEARANCE OF PLASMA CHYLOMICRON REMNANTS

Dietary lipid, following incorporation into chylomicrons, is rapidly removed from the blood by a two-stage process. Most of the triglyceride is taken up by extrahepatic tissue, particularly muscle and adipose tissue. The residual triglyceride and virtually all of the cholesterol ester is removed by the liver through the clearance of a particle called a chylomicron remnant. The remarkable rapidity and specificity of uptake of this particle seems to be due to its acquisition of apoE in the plasma. Uptake is mediated in part by the LDL receptor, the LRP (α(a)-macroglobulin receptor), and perhaps by a sieving mechanism that leads to trapping, but not endocytosis. Uptake is modulated by the type of apoE inherited, the amount of apoC present on the particle, and, perhaps, the phospholipid and fatty acyl chain composition of the particle. The process may be slowed in diabetes and hypothyroidism. The metabolic effects of the particle can be variable, depending on the composition of the diet, and this can affect whole body cholesterol metabolism significantly. Furthermore, even moderately prolonged residence of these particles in the circulation could contribute in a significant way to atherogenesis. Thus, the remnant particle and its uptake by the liver may be important links in determining the dietary contribution to the rate of atherosclerosis.