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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3041-3048.)
© 1997 American Heart Association, Inc.

Articles

Suppression of Lipid Transfer Inhibitor Protein Activity by Oleate

A Novel Mechanism of Cholesteryl Ester Transfer Protein Regulation by Plasma Free Fatty Acids

Richard E. Morton; ; Diane J. Greene

From the Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

Correspondence to Richard E. Morton, PhD, Department of Cell Biology, NC10, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail mortonr{at}cesmtp.ccf.org

Abstract Cholesteryl ester transfer protein (CETP) mediates the interlipoprotein exchange of cholesteryl ester (CE) and triglyceride. A second plasma protein, lipid transfer inhibitor protein (LTIP), binds to lipoproteins and inhibits CETP activity by displacing CETP from the lipoprotein surface. Since free fatty acids (FFAs) enhance the binding of CETP to lipoproteins, we have examined the possible role of FFAs in modulating LTIP activity. Partially purified CETP, LTIP, and lipoproteins were incubated with 0 to 30 µmol/L sodium oleate, and the transfer of CE between a labeled donor lipoprotein and a given acceptor lipoprotein was measured. Without LTIP, oleate stimulated CETP-mediated CE transfer between VLDL, LDL, and HDL up to threefold. This stimulation was unique in both magnitude and oleate concentration dependence for each donor-acceptor lipoprotein pair. In contrast to CETP activity, in transfer reactions involving LDL or VLDL as donor, LTIP activity was suppressed (>80%) by 10 to 15 µmol/L oleate. LTIP activity in transfer reactions with HDL as donor was less sensitive. Similar results to these were observed when lipid transfer reactions were measured in the total lipoprotein fraction isolated from FFA-enriched plasma. The FFA content of lipoproteins was strongly influenced by the concentration of FFA in plasma; lipoprotein FFA levels sufficient to suppress LTIP activity by 50% to 100% were achieved in plasma containing 0.8 to 1.0 mmol/L FFA. We conclude that LTIP may be functionally inactive during periods of transient elevations of plasma FFA levels, such as during postprandial lipemia or overnight fasting, or chronically suppressed in disease states in which plasma FFA levels are increased. The suppression of LTIP activity by FFA allows for maximum CETP-mediated lipid transfer between all lipoproteins, including lipid transfer reactions involving LDL that are normally preferentially suppressed by LTIP.

Key Words: cholesteryl ester transfer protein • lipid transfer inhibitor protein • free fatty acid

This article has been cited by other articles:

				R. E. Morton and D. J. Greene CETP and lipid transfer inhibitor protein are uniquely affected by the negative charge density of the lipid and protein domains of LDL J. Lipid Res., December 1, 2003; 44(12): 2287 - 2296. [Abstract] [Full Text] [PDF]

				X. Wang, D. M. Driscoll, and R. E. Morton Molecular Cloning and Expression of Lipid Transfer Inhibitor Protein Reveals Its Identity with Apolipoprotein F J. Biol. Chem., January 15, 1999; 274(3): 1814 - 1820. [Abstract] [Full Text] [PDF]