HDL biology
Meal-induced CETP activity redirects HDL cholesterol esters toward atherogenic VLDL-1 particles, rising 32-fold in type IIB hyperlipidemia versus healthy controls (J Lipid Res 2002)
Original title: Cholesteryl ester flux from HDL to VLDL-1 is preferentially enhanced in type IIB hyperlipidemia in the postprandial state
In 12 subjects with type IIB hyperlipidemia and 14 normolipidemic controls, cholesteryl ester (CE) transfer from HDL to triglyceride-rich lipoproteins was measured after a 1200 kcal mixed meal. Free cholesterol efflux via the SR-BI receptor rose 23% at 4 h postprandially in the IIB group (P < 0.005) but was unchanged in controls. In IIB subjects, total CE transfer from HDL rose from 15 +/- 2 to 28 +/- 2 microg CE/h/ml at 4 h (+87%; P = 0.0004), with transfer to chylomicrons and VLDL-1 preferentially stimulated 2.6-fold and 2.3-fold. Over the 8 h postprandial period, CETP-mediated CE flux from HDL to VLDL-1 rose 32-fold versus controls (P < 0.005), directing HDL cholesteryl ester toward formation of atherogenic remnant particles.
Original abstract
Postprandial triglyceride-rich lipoproteins (TRL) exert proatherogenic effects at the arterial wall, including lipid deposition. Following consumption of a mixed meal (1200 kcal), plasma-mediated cellular free cholesterol (FC) efflux, lecithin:cholesterol acyltransferase (LCAT), and cholesteryl ester transfer protein (CETP) activities were determined in subjects (n = 12) displaying type IIB hyperlipidemia and compared with those in a normolipidemic control group (n = 14). The relative capacity of plasma to induce FC efflux from Fu5AH cells via the SR-BI receptor was significantly increased 4 h postprandially (+23%; P < 0.005) in the type IIB group, whereas it remained unchanged for postprandial plasma from normolipidemic subjects. LCAT activity was significantly elevated 2 h postprandially in both the IIB and control groups, (+46% and +36%, respectively; P < 0.005 vs. respective baseline value). In type IIB subjects, total cholesteryl ester (CE) mass transfer from HDL to total TRL [chylomicrons (CMs) + VLDL-1 + VLDL-2 + IDL] increased progressively from 15 +/- 2 micro g CE/h/ml at baseline to 28 +/- 2 micro g CE transferred/h/ml (+87%; P = 0.0004) at 4 h postprandially. CE transfer to CMs and VLDL-1 was preferentially stimulated (2.6-fold and 2.3-fold respectively) at 4 h in IIB subjects and occurred concomitantly with elevation in mass and particle number of both CMs (2.3-fold) and VLDL-1 (1.3-fold). Furthermore, in type IIB subjects, CETP-mediated total CE flux over the 8 h postprandial period from HDL to potentially atherogenic TRL was significantly enhanced, and notably to VLDL-1 (32-fold elevation; P < 0.005), relative to control subjects. Such CE transfer flux was reflected in a significant postprandial increase in CE-TG ratio in both CMs and VLDL-1 in type IIB plasmas. In conclusion, HDL-CE is preferentially targeted to VLDL-1 via the action of CETP during alimentary lipemia, thereby favoring formation and accumulation of atherogenic CE-rich remnant particles.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.