Large buoyant LDL-like particles in hepatic lipase deficiency

Hepatic lipase (HL) is thought to play a role in processing very low density lipoprotein to low density lipoprotein (LDL). To analyze the relationship between HL and LDL, the density, size, and chemical composition of LDL isolated from 18 normal subjects and from three subjects with reduced or absent levels of HL activity were compared. In an HL-deficient subject, the major peak of apoprotein (apo) B-containing lipoproteins ('LDL') had a density of 1.023 g/ml and a diameter of 26.4 nm compared to male control subjects (1.044 +/- 0.006 g/ml and 25.3 +/- 0.3 nm). Two half-sisters of the HL-deficient subject with half the normal levels of HL activity had LDL that also were more buoyant and slightly larger than the LDL isolated from female control subjects. The peak density and average diameter of LDL were correlated with HL activity, consistent with the hypothesis that HL influenced formation and physical characteristics of typical LDL. Apo B-100 was the major apoprotein in the 'LDL' isolated from the HL-deficient subject and contained a greater proportion of triglyceride compared to the control subjects' LDL. The absence of HL appears to prevent the production of classical LDL. Our data support the hypothesis that HL helps determine normal LDL characteristics.