HDL biology
The inability of rat serum to transfer dietary oxidized cholesterol to LDL/HDL points to CETP as the mediator (J Lipid Res 2003)
Original title: Oxidized cholesterol in the diet is a source of oxidized lipoproteins in human serum
Researchers fed six controls and three patients with type III hyperlipoproteinemia a meal containing 400 mg of oxidized cholesterol (alpha-epoxy cholesterol) to test whether dietary oxidized cholesterol is absorbed and enters circulating lipoproteins. Alpha-epoxy cholesterol appeared in chylomicron/chylomicron remnants (CM/RM) and endogenous VLDL, LDL, and HDL in both groups; in controls it cleared from CM/RM within 10 hours but persisted in endogenous lipoproteins for 72 hours, while type III patients retained it mainly in CM/RM. Incubating CM/RM containing alpha-epoxy cholesterol with human LDL and HDL produced rapid transfer of the oxidized cholesterol to both, but substituting rat serum, which naturally lacks CETP, abolished this transfer, implicating cholesteryl ester transfer protein as the mediator. LDL that had acquired alpha-epoxy cholesterol also showed increased susceptibility to further copper-induced oxidation, leading the authors to conclude that dietary oxidized cholesterol may accelerate atherosclerosis by raising oxidized cholesterol levels in circulating LDL and chylomicron remnants.
Original abstract
The aim of this study was to determine in humans whether oxidized cholesterol in the diet is absorbed and contributes to the pool of oxidized lipids in circulating lipoproteins. When a meal containing 400 mg cholestan-5alpha,6alpha-epoxy-3beta-ol (alpha-epoxy cholesterol) was fed to six controls and three subjects with Type III hyperlipoproteinemia, alpha-epoxy cholesterol in serum was found in chylomicron/chylomicron remnants (CM/RM) and endogenous (VLDL, LDL, and HDL) lipoproteins. In controls, alpha-epoxy cholesterol in CM/RM was decreased by 10 h, whereas in endogenous lipoproteins it remained in the circulation for 72 h. In subjects with Type III hyperlipoproteinemia, alpha-epoxy cholesterol was mainly in CM/RM. In vitro incubation of the CM/RM fraction containing alpha-epoxy cholesterol with human LDL and HDL that did not contain alpha-epoxy cholesterol resulted in a rapid transfer of oxidized cholesterol from CM/RM to both LDL and HDL. In contrast, no transfer was observed when human serum was substituted with rat serum, suggesting that cholesteryl ester transfer protein is mediating the transfer. Thus, alpha-epoxy cholesterol in the diet is incorporated into the CM/RM fraction and then transferred to LDL and HDL, contributing to lipoprotein oxidation. Moreover, LDL containing alpha-epoxy cholesterol displayed increased susceptibility to further copper oxidation in vitro. It is possible that oxidized cholesterol in the diet accelerates atherosclerosis by increasing oxidized cholesterol levels in circulating LDL and chylomicron remnants.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.