American Journal of Clinical Nutrition, Vol 65, 1581S-1589S, Copyright © 1997 by The American Society for Clinical Nutrition, Inc

REVIEW ARTICLES

Theoretical considerations of what regulates low-density-lipoprotein and high-density-lipoprotein cholesterol

JM Dietschy
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8887, USA.

The concentration of cholesterol carried in low-density-lipoprotein cholesterol (LDL-C) is predominantly dictated by metabolic events occurring in liver. LDL-C is derived from the intravascular metabolism of very-low-density lipoproteins, and, in every species, this lipoprotein particle is predominantly cleared by liver through receptor- dependent mechanisms. In addition to cholesterol absorbed from the diet, sterol is also synthesized within the body and this synthesis occurs predominantly in extrahepatic organs. When the amount of cholesterol input into the body is increased, there is expansion of the pools of sterol within liver cells and down-regulation of the receptors responsible for clearing LDL-C from the bloodstream. As a consequence, the concentration of LDL-C in plasma increases. When dietary cholesterol intake is kept constant, some long-chain saturated fatty acids further suppress hepatic LDL receptor activity whereas several unsaturated fatty acids have the opposite effect. These regulatory events are apparently articulated through the ability of these fatty acids to shift intracellular cholesterol between a regulatory and a storage pool. High-density lipoproteins, in contrast, function primarily to move excess cholesterol from the extrahepatic organs to liver for excretion. Although the concentration of high-density- lipoprotein cholesterol in the plasma may be influenced by the rate of apolipoprotein A-I production or the activity of cholesterol ester transfer protein, it is less clear whether dietary long-chain fatty acids have any effect on these processes. The regulatory effects of the saturated and unsaturated long-chain fatty acids on LDL-C concentrations can be shown in a variety of experimental animals and also in humans.

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