Article

Cholesterol transport between cells and high density lipoprotein subfractions from obese and lean subjects

Correspondence to: Dmitri Sviridov.

We studied the pathway of cholesterol efflux from fibroblasts by testing plasma samples from obese and lean subjects. Plasma samples were incubated with [³H]cholesterol-labeled human skin fibroblasts for 1 h to ensure uniform labeling of all of the high density lipoprotein (HDL) subfractions. Supernatants were then transferred to unlabeled cells and 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 content of total apolipoprotein A-I (apoA-I) and ₁-HDL and a lower overall capacity to take up labeled cholesterol. In plasma of lean subjects, pre ß₂-HDL and ₁-HDL appeared to be the most active particles in the initial uptake of unlabeled cellular cholesterol. By contrast, in plasmas of obese subjects, the pre ß₁-HDL appeared to be most active in taking up unlabeled cellular cholesterol and transferring [³H]cholesterol. There were negative correlations between body mass index (BMI) and apoA-I and ₁-HDL concentrations, and with the apparent increments of cellular cholesterol uptake within pre ß₂-HDL and ₁-HDL, as well as with the overall capacity to promote cholesterol efflux. By contrast, BMI was positively correlated with the apparent increment in cellular cholesterol within pre ß₁-HDL. While cholesterol efflux was correlated with total plasma apoA-1, there were no such correlations with the concentration of any individual HDL subfraction.

We conclude that the pattern of cholesterol transfer between fibroblasts and high density lipoprotein particles is influenced by body fatness and may be a factor in the abnormal metabolism of HDL in obesity.—Sasahara, T., P. Nestel, N. Fidge, and D. Sviridov. Cholesterol transport between cells and high density lipoprotein subfractions from obese and lean subjects. J. Lipid Res. 1998. 39: 544–554.

Supplementary key words: cholesterol efflux, obesity, high density lipoprotein, preß-HDL, apolipoprotein A-I, human plasma, lipoproteins, reverse cholesterol transport

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