The role of apolipoprotein A-I and apolipoprotein A-II in high-density lipoprotein binding to human adipocyte plasma membranes

Abstract

Adipocyte plasma membranes purified from omental fat tissue biopsies of massively obese subjects possess specific binding sites for high-density lipoprotein (HDL 3). This binding was independent of apolipoprotein E as HDL 3 isolated from plasma of an apolipoprotein E-deficient individual was bound to a level comparable to that of normal HDL 3. To examine the importance of apolipoprotein A-I, the major HDL 3 apolipoprotein, in the specific binding of HDL 3 to human adipocytes, HDL 3 modified to contain varying proportions of apolipoproteins A-I and A-II was prepared by incubating normal HDL 3 particles with different amounts of purified apolipoprotein A-II. As the apolipoproteins A-I-to-A-II ratio in HDL 3 decreased, the binding of these particles to adipocyte plasma membranes was reduced. Compared to control HDL 3, a 92 ± 3.1% reduction (mean ± S. E., n = 3) in maximum binding capacity was observed along with an increased binding affinity for HDL 3 particles in which almost all of the apolipoprotein A-I had been replaced by A-II. The uptake of HDL cholesteryl ester by intact adipocytes as monitored by [ 3H] cholesteryl ether labeled HDL 3, was also significantly reduced (about 35% reduction, P < 0.005) by substituting apolipoprotein A-II for A-I in HDL 3. These data suggest that HDL binding to human adipocyte membranes is mediated primarily by apolipoprotein A-I and that optimal delivery of cholesteryl ester from HDL to human adipocytes is also dependent on apolipoprotein A-I.