FREE FATTY-ACIDS MODULATE LDL RECEPTOR ACTIVITY IN BHK-21-CELLS

It has been shown that dietary fatty acids affect serum low density li poprotein (LDL) levels, but the mechanism responsible for this effect is still under debate. Here we investigate the effect of different fre e fatty acids on LDL receptor activity in BHK-21 cells. These cells po ssess a classical LDL receptor strongly regulated by substances like 2 5-OH-cholesterol or lovastatin. Preincubation of cells for 24 h with b oth oleic (cis 18:1) and its trans counterpart, elaidic acid, enhanced I-125-LDL binding, internalization and degradation, being oleic acid more effective than elaidic acid. Among polyunsaturated fatty acids (P UFA) of the n-6 series arachidonic acid (20:4) enhanced LDL receptor a ctivity more than linoleic acid (18:2), and among PUFA of the n-3 seri es docosahexaenoic (22:6) and eicosapentaenoic acids (20:5) were more effective compared to a-linolenic acid (18:3). Conversely, preincubati on of cells with saturated fatty acids, palmitic (16:0) and stearic (1 8:0) acids, decreased binding, internalization and degradation of I-12 5-LDL. Scatchard analysis of binding data obtained with palmitic and o leic acids showed that these two fatty acids affect LDL receptor numbe r without altering receptor affinity. The regulatory effect of free fa tty acids on LDL receptor activity in BHK-21 cells is consistent with the hypothesis that the ability of fatty acids to modulate LDL-cholest erol levels in vivo is mediated, at least in part, by an action on rec eptor-dependent uptake of LDL. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.