Oleic, linoleic and linolenic acids enhance receptor-mediated uptake of low density lipoproteins in Hep-G2 cells

In the present study, the binding, internalization and degradation of low-density lipoprotein (LDL) was investigated in Hep-G2 cells treated with 18:0, 18:1, 18:2 and 18:3. In non-treated control cells, the surface binding (heparin-releasable) of 125I-LDL progressed in a saturable manner reaching equilibrium within 2 h, amounting 24.0 ± 1.1, 29.5 ± 1.3 and 31.4 ± 2.8 (ng/mg cell protein) at 1, 2 and 4 h, respectively. The cells rapidly internalized 125I-LDL reaching a plateau at 2 h (72.4 ± 6.3/1 h, 96.7 ± 4.3/2 h and 100.8 ± 4.6 ng/mg protein/4 h, respectively). The degradation of internalized LDL progressed slowly during the first hour of incubation reflecting the time required to an uptake and delivery of LDL to the cellular lysosomes. The levels of degraded LDL discharged into the medium then increased rapidly in a linear manner after the initial lag period, amounting 16.8 ± 1.2, 51.8 ± 7.0 and 118.2 ± 5.7 ng/mg protein at 1, 2 and 4 h, respectively. The treatment of cells with of 1.0 mM of fatty acids for 4 h resulted in a significant increase in the surface binding of 125I-LDL compared to the control (34.9 ± 3.0), but it was significantly lower in cells exposed to 18:0 (48.2 ± 2.0) than to 18:1 (56.8 ± 5.1), 18:2 (56.0 ± 3.5) and 18:3 (57.8 ± 6.0 ng/mg protein/4 h) (P < 0.05). The levels of degraded LDL in cells remained nearly the same regardless of fatty acid treatments, but degraded LDL levels in the medium were much higher in cells exposed to 18:1 (167.6 ± 10.1), 18:2 (159.8 ± 7.7) and 18:3 (165.1 ± 14.7) than to 18:0 (142.1 ± 8.4) and the control (121.2 ± 3.4 ng/mg protein/4 h) (P < 0.05). The present finding that 18:1 is equally effective in enhancing the receptor-mediated LDL uptake and its degradation as those of 18:2 and 18:3 suggests that the major action of 18:1 in lowering LDL-cholesterol levels also involves an increased clearance of LDL via hepatic LDL-receptors. [Copyright &y& Elsevier]