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Regulation of rat hepatic cholesterol metabolism. Effects of lipoprotein composition on acyl coenzyme A:cholesterol acyltransferase in vivo and in the perfused liver and on hepatic cholesterol secretion.

Lipoproteins that are removed from the circulation by the liver can deliver both cholesterol and triglycerides to the hepatocyte. Relative proportions of these lipids may vary in lipoproteins and, thus, their uptake may have differing effects on cholesterol homeostasis. To study this, lipoproteins containing the same amounts of cholesterol but different amounts of triglyceride were administered to intact rats or to an isolated perfused rat liver. The responses of acyl coenzyme A:cholesterol acyltransferase (ACAT), very low density lipoprotein (VLDL) triglyceride and cholesterol secretion, and biliary cholesterol content were examined after 2 hr. Administration of triglyceride-rich chylomicrons (average triglyceride:cholesterol = 136.5 by mass) in vivo or their remnants (average triglyceride:cholesterol = 32.7 by mass) to the perfused liver resulted in an 80% decrease in ACAT activity. In the perfused liver system, VLDL cholesterol and triglyceride secretion was increased while biliary cholesterol content decreased. Administration of standard chylomicrons (average triglyceride:cholesterol = 33.9 by mass) or their remnants (average triglyceride:cholesterol = 11.4 by mass) lowered ACAT activity by 24% in vivo, but had no significant effect on any of the parameters measured in the perfused liver system. Administration of cholesterol-rich VLDL (average triglyceride:cholesterol = 0.47 by mass) in vivo increased ACAT activity 1.4-fold, but administration of their remnants (average triglyceride:cholesterol = 0.17 by mass) had little effect on any of the parameters measured in the perfused liver. Thus, the lipid composition of lipoproteins removed by the liver elicited acute responses by parameters important in the maintenance of hepatic cholesterol homeostasis. These responses reflected the net effects of both the cholesterol and the triglyceride contents of the particles.