CHOLESTEROL TRANSPORT BETWEEN CELLS AND HIGH-DENSITY-LIPOPROTEIN SUBFRACTIONS FROM OBESE AND LEAN SUBJECTS

We studied the pathway of cholesterol efflux from fibroblasts by testi ng plasma samples from obese and lean subjects. Plasma samples were in cubated with [H-3]cholesterol-labeled human skin fibroblasts for 1 h t o ensure uniform labeling of all of the high density lipoprotein (HDL) subfractions. Supernatants were then transferred to unlabeled cells a nd the displacement of labeled cholesterol within HDL subfractions by unlabeled cellular cholesterol was analyzed in short-term experiments. Plasma samples of obese subjects were characterized by a lower conten t of total apolipoprotein A-I (apoA-I) and alpha(1)-HDL and a lower ov erall capacity to take up labeled cholesterol. In plasma of lean subje cts, pre beta(2)-HDL and alpha(1)-HDL appeared to be the most active p articles in the initial uptake of unlabeled cellular cholesterol. By c ontrast, in plasmas of obese subjects, the pre beta(1)-HDL appeared to be most active in taking up unlabeled cellular cholesterol and transf erring [H-3]cholesterol. There were negative correlations between body mass index (BMI) and apoA-I and alpha(1)-HDL concentrations, and with the apparent increments of cellular cholesterol uptake within pre bet a(2)-HDL and alpha(1)-HDL, as well as with the overall capacity to pro mote cholesterol efflux. By contrast, BMI was positively correlated wi th the apparent increment in cellular cholesterol within pre beta(1)-H DL. While cholesterol efflux was correlated with total plasma apoA-I, there were no such correlations with the concentration of any individu al HDL subfraction. We conclude that the pattern of cholesterol transf er between fibroblasts and high density lipoprotein particles is influ enced by body fatness and may be a factor in the abnormal metabolism o f HDL in obesity.