Free fatty acids modulate LDL receptor activity in BHK-21 cells.
It has been shown that dietary fatty acids affect serum low density lipoprotein (LDL) levels, but the mechanism responsible for this effect is still under debate. Here we investigate the effect of different free fatty acids on LDL receptor activity in BHK-21 cells. These cells possess a classical LDL receptor strongly regulated by substances like 25-OH-cholesterol or lovastatin. Preincubation of cells for 24 h with both oleic (cis 18:1) and its trans counterpart, elaidic acid, enhanced 125I-LDL binding, internalization and degradation, being oleic acid more effective than elaidic acid. Among polyunsaturated fatty acids (PUFA) of the n-6 series arachidonic acid (20:4) enhanced LDL receptor activity more than linoleic acid (18:2), and among PUFA of the n-3 series docosahexaenoic (22:6) and eicosapentaenoic acids (20:5) were more effective compared to alpha-linolenic acid (18:3). Conversely, preincubation of cells with saturated fatty acids, palmitic (16:0) and stearic (18:0) acids, decreased binding, internalization and degradation of 125I-LDL. Scatchard analysis of binding data obtained with palmitic and oleic acids showed that these two fatty acids affect LDL receptor number without altering receptor affinity. The regulatory effect of free fatty acids on LDL receptor activity in BHK-21 cells is consistent with the hypothesis that the ability of fatty acids to modulate LDL-cholesterol levels in vivo is mediated, at least in part, by an action on receptor-dependent uptake of LDL.
Bucci
C
C
Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano and Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Napoli, Italy.
Serù
R
R
Annella
T
T
Vitelli
R
R
Lattero
D
D
Bifulco
M
M
Mondola
P
P
Santillo
M
M
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006888:Hydroxycholesterols / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism*
D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011973:Receptors, LDL; C007997:25-hydroxycholesterol; D008148:Lovastatin; D007770:L-Lactate Dehydrogenase