Oleate and Other Long Chain Fatty Acids Stimulate Low Density Lipoprotein Receptor Activity by Enhancing Acyl Coenzyme A:Cholesterol Acyltransferase Activity and Altering Intracellular Regulatory Cholesterol Pools in Cultured Cells

• Published in: The Journal of biological chemistry Vol. 270; no. 17; pp. 10008 - 10016
• Main Authors: Rumsey, S C, Galeano, N F, Lipschitz, B, Deckelbaum, R J
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 28-04-1995
• Subjects: Cells, Cultured; Cholesterol - metabolism; Cholesterol Esters - pharmacology; Enzyme Activation; Fatty Acids, Nonesterified - pharmacology; Humans; Lipoproteins, LDL - metabolism; Oleic Acid; Oleic Acids - pharmacology; Protein Binding; Receptors, LDL - drug effects; Receptors, LDL - metabolism; Sterol O-Acyltransferase - metabolism; Triglycerides - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.17.10008

Modification of dietary fatty acid composition results in changes in plasma cholesterol levels in man. We examined the effect
of in vitro fatty acid supplementation on low density lipoprotein (LDL) receptor activity in cultured cells and questioned whether changes
were related to fatty acid-induced alterations in acyl-CoA:cholesterol acyltransferase (ACAT) activity. Preincubation of cultured
cells ( i.e. human skin fibroblasts, J774 macrophages, and HepG2 cells) with oleic acid (oleic acid:bovine serum albumin molar ratio 2:1)
at 37°C for longer than 2 h resulted in a 1.2- to 1.5-fold increase in LDL cell binding at 4°C and LDL cell degradation at
37°C. Scatchard analysis showed that oleic acid increased LDL receptor number but not LDL affinity ( K ). Fatty acid supplementation of J774 macrophages increased both LDL receptor activity and cholesteryl ester accumulation.
The ACAT inhibitor, 58-035, eliminated both effects, and increased ACAT activity preceded stimulation of LDL receptor activity
by 1-2 h. Supplementation of macrophages with triolein emulsion particles also increased LDL cell binding and degradation,
and addition of cholesterol to the emulsions abolished this effect. Among fatty acids tested, oleate (18:1), arachidonate
(20:4), and eicosapentanoate (20:5) demonstrated the greatest effects. We hypothesize that certain fatty acids delivered to
cells either in free form, or as triglyceride, first increase cellular ACAT activity, which then causes a decrease in an intracellular
free cholesterol pool, signaling a need for increased LDL receptor activity. This mechanism may play a role in the effect
of certain dietary fatty acids on LDL metabolism in vivo .