ALTERED PROPERTIES OF HIGH-DENSITY-LIPOPROTEIN SUBFRACTIONS IN OBESE SUBJECTS

Human HDL are heterogeneous in their metabolism and comprise small, na scent pre-beta-HDL and mole mature alpha-HDL. Evidence exists that pre -beta(1)-HDL is the initial acceptor of cellular free cholesterol, whi ch then transfers sequentially to other pre-beta species and then, aft er esterification, into alpha-HDL. As HDL particles are themselves tra nsformed during this process, we postulated that in disorders in which HDL-cholesterol is low, such as obesity, the distribution of HDL part icles may be disturbed. In this study, we analyzed the HDL profile in 23 obese and 18 lean subjects, and further investigated the effects of dietary change in 15 obese subjects. HDL were separated by two-dimens ional nondenaturing electrophoresis and the apoA-I content in each fra ction was quantified, alpha(1)-HDL in obese subjects was significantly lower (P < 0.001) and alpha(2)-, alpha(3)-, and pre-beta(1)-HDL were significantly higher (P < 0.05 for alpha(2)-HDL, P < 0.001 for alpha(3 )- and pre-beta(1)-HDL) than in lean subjects. On stepwise regression analysis, body mass index accounted for 52% (negatively) of the varian ce in alpha(1)-HDL and for 16% and 33% (positively) for the variances in alpha(3)- and pre-beta(1)-HDL, respectively. alpha(1)- and pre-beta (3)-HDL increased significantly after low-fat, oleic acid-rich, or alp ha-linolenic acid-rich diets. The profile of alpha-HDL particles and a lso of pre-beta-HDL, particles therefore shifted to smaller species in obese subjects, and this was influenced by dietary fat. Increased pre -beta(1)-HDL-apoA-I in obese subjects is likely to derive from increas ed HDL catabolism but may also reflect diminished transformation of pr e-beta(1)- to pre-beta(2)-HDL which might reduce capacity for reverse cholesterol transport and partly explain lower HDL-cholesterol levels.