Multifunctional role for fetuin (fetal protein) in lipid transport

Recent studies from this laboratory have shown that fetuin 1) is nearly 50-fold more efficient than albumin in incorporating exogenous fatty acids into cultured cells, (JBC, 265: 5883, 1990), and 2) is associated with a lipoprotein-like particle (FASEB J. 3: 2075-2080, 1989). In the present study, this lipid-containing fraction (FLP) was isolated by ultracentrifugation, and its effect on cholesterol efflux from cultured human skin fibroblasts and Hep-G2 cells prelabeled with [14C]cholesterol was investigated. FLP fraction caused a significant efflux of [14C]cholesterol from cells, the same in magnitude as HDL. This effect of fetuin supranatant fraction increased proportionately with concentration and time. Similar results were observed with Hep-G2 cells. This ability to induce efflux of cholesterol was confirmed by a decrease in cholesterol mass of cells after 24 h incubation with FLP. The ultracentrifugal bottom (infranatant) fraction of fetuin (FI) was ineffective in this regard. However, FI was more effective in the incorporation of exogenous fatty acids into cellular triglycerides. These studies suggest that the fetuin molecule is a multifunctional protein (delivery of fatty acids to cells and cholesterol efflux from cells) which may play a role in lipid transport during fetal life.