HDL biology
Oleate suppresses LTIP activity over 80%, unleashing maximal CETP-mediated lipid transfer between all lipoproteins including LDL (Arterioscler Thromb Vasc Biol 1997)
Original title: Suppression of lipid transfer inhibitor protein activity by oleate. A novel mechanism of cholesteryl ester transfer protein regulation by plasma free fatty acids
CETP mediates cholesteryl ester and triglyceride exchange between lipoproteins, while lipid transfer inhibitor protein (LTIP) binds lipoproteins and inhibits CETP by displacing it from the lipoprotein surface. Testing whether free fatty acids (FFAs), which enhance CETP-lipoprotein binding, also modulate LTIP, the authors incubated CETP, LTIP, and lipoproteins with 0 to 30 micromol/L sodium oleate. Without LTIP, oleate stimulated CETP-mediated cholesteryl ester transfer between VLDL, LDL, and HDL up to threefold. In reactions with LDL or VLDL as donor, LTIP activity was suppressed by more than 80% at 10 to 15 micromol/L oleate, while LTIP activity with HDL as donor was less sensitive. The authors conclude LTIP becomes functionally inactive during transient FFA elevations, permitting maximal CETP-mediated lipid transfer, including reactions involving LDL that LTIP normally suppresses.
Original 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 mumol/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 mumol/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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.