Apolipoprotein A-II Influences the Substrate Properties of Human HDL 2 and HDL 3 for Hepatic Lipase

Abstract

Hepatic lipase has a demonstrated dual role in plasma lipid transport in that it participates in the removal of remnants of triglyceride-rich lipoproteins from the circulation and in the metabolism of plasma HDL. The study presented here investigated the substrate properties for hepatic lipase of HDL differing in density and apolipoprotein (apo) composition. Rates of fatty acid liberation were twofold higher in HDL ₂ compared with the respective HDL ₃ subspecies. Within each density class, enzyme-catalyzed fatty acid release was nearly twofold higher from HDL containing apoA-II compared with HDL devoid of apoA-II. When native HDL ₃ devoid of apoA-II was reconstituted with dimeric apoA-II in vitro, rates of fatty acid liberation in reconstituted particles were similar to those in native HDL ₃ containing apoA-II. HDL containing apoA-II competed more effectively with small VLDL for binding of hepatic lipase than HDL devoid of apoA-II. HDL ₃ , particularly apoA-II–containing HDL ₃ , reduced lipolysis of triglyceride and total fatty acid liberation in small VLDL. We conclude that the substrate properties of HDLs for hepatic lipase are influenced by both their size and apoA-II content. Moreover, size as well as apoA-II content may indirectly affect remnant clearance.