Formation of cholesteryl ester-rich particulate lipid during metabolism of chylomicrons

The metabolism of chylomicrons doubly labeled with cholesterol-(3)H and triglyceride-(14)C was studied in unanesthetized rats which were absorbing a fatty test meal. 10 min after intravenous injection, 80% of chylomicron cholesteryl ester, but only 20% of chylomicron triglyceride, was found in the liver. Treatment of recipient rats with puromycin to block hepatic triglyceride release did not increase the proportion of chylomicron triglyceride found in the liver. Rapid partition of chylomicron triglyceride from cholesterol ester also occurred in rats in which the liver had been excluded from the circulation. However, now the cholesteryl ester accumulated in the plasma, whereas triglyceride was cleared by peripheral tissues. Residual labeled cholesterol in the plasma of such rats was shown to be present in particulate form, together with some residual triglyceride. The remnant particles contained about 13% cholesteryl ester. When injected into other rats the remnant particles appeared in the liver more rapidly than did chylomicrons.These observations were consistent with the hypothesis that the first step in chylomicron metabolism occurred in extrahepatic tissues where a large portion of the triglyceride was removed by the action of lipoprotein lipase. The remnant particles so produced contained the chylomicron cholesteryl ester and residual triglyceride, and they were removed from the plasma by the liver.