The effects of di- and triacylglycerols on the charge, stability and conformation of HDL and on hepatic lipase activity.

Abstract

Alterations in HDL composition that occur in the hypertriglyceridemic state may modulate a number of events involved in cholesterol homeostasis. To elucidate the details of how HDL neutral acylated glycerol (NAG) composition can affect the molecular structure of HDL particles, the charge, conformation and stability of apoA-I have been investigated in homogeneous recombinant HDL particles (Lp2A-I) containing phosphatidylcholine (POPC), triolein (TG) and/or diolein (DG). The effect of HDL composition and structure on the hydrolysis of HDL phospholipids, DG and TG by hepatic lipase (HL) has also been investigated in native and Lp2A-I. In summary, DG causes specific conformational changes to apoA-I that give rise to a decrease in the particle surface potential and increase in stability. Together, these structural changes appear to regulate the actions of HL; HDL-DG content regulates the hydrolysis of phospholipid (PL), DG and TG by HL. The data indicates that hepatic lipase acts primarily as a surface lipid lipase with HDL particles and that DG is the preferred substrate of HL in HDL. (Abstract shortened by UMI.)