Nineteen young male normolipidemic volunteers sequentially consumed three test meals consisting of cream only, sucrose only, or cream with sucrose. These oral fat-tolerance tests showed an amplification of the postprandial excursion of serum triglyceride and cholesterol concentrations when sucrose was included in a lipid-rich meal compared with both the cream-only meal and the sucrose-only meal. The triglyceride concentration increase occurred only in the late postprandial phase whereas the cholesterol concentration was increased for the entire 8 h studied. The increased triglyceride and cholesterol concentrations in the triglyceride-rich lipoprotein (TRL) fraction accounted for most of the increase. The clearance of an intravenous lipid emulsion was measured before and 2 and 4 h after a sucrose meal. The two postprandial clearance rates were 34% slower than the fasting value. These data indicate that sucrose-induced postprandial hypertriglyceridemia may be induced by an inhibition of the clearance of triglyceride. The slower rate of lipolysis may cause the accumulation of cholesterol in TRL.

The rate of degradation of low-density-lipoprotein (LDL) receptors was measured in cultured human skin fibroblasts by [35S]methionine pulse-chase experiments. The half-life of LDL receptors was unaltered by inclusion of LDL in the medium (t1/2 11 h). Neither lysosomotropic inhibitors (chloroquine or NH4Cl) nor leupeptin inhibited the rate of receptor degradation in the absence of ligand. In cells incubated at 18 degrees C to inhibit the delivery of internalized ligands from endocytic vesicles to lysosomes, receptor degradation continued, but at the expected rate of about six times lower than that at 37 degrees C. Mutant LDL receptors defective in internalization were degraded at the same rate as normal receptors, suggesting that receptor internalization and recycling are not required for basal turnover. We conclude that the rate-limiting steps for, and probably the whole pathway of, degradation of normal LDL receptors does not take place in lysosomes.

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