High density lipoproteins regulate the displacement of hepatic lipase activity

Abstract

ApoA-I and HDL readily displace cell surface-bound HL and stimulate TG-hydrolysis by HL. To evaluate the regulatory effect of HDL structure on HL displacement, cell culture experiments using the native and reconstituted HDL were undertaken. Structural features of HDL such as size, density, and chemical composition were found to be important regulators of HL displacement. The larger, more buoyant HDL were stimulatory to HL displacement, whereas the smaller denser particles were inhibitory. Apolipoprotein and lipid composition had a direct regulatory role in HL displacement. Apolipoprotein A-II increased HL displacement significantly. Apolipoprotein C-I also increased the displacement, but in a lesser degree than apolipoprotein A-II. Phospholipid content of HDL was inhibitory regardless of the electrostatic charge of the HDL particle. The triglyceride component of HDL had the most significant inhibitory role in HL displacement and blocked the displacement almost completely. In addition, TG-enriched HDL fractions from hypertriglyceridemic/hypercholesterolemic subjects were unable to displace HL from the cell surface. In summary, these results show that the structure and composition of HDL particles in plasma are central to regulation of HL displacement and, thereby, regulate the hydrolytic activity of HL.