Dependence of metabolic and structural heterogeneity of cholesterol ester-rich very low density lipoproteins on the duration of cholesterol feeding in rabbits.

Cholesterol ester-rich (CER) VLDL accumulate rapidly in the plasma of rabbits fed cholesterol-enriched diets.However, the major loci of enhanced synthesis of subfractions of CER- VLDL, their interaction with macrophages, and their relative contribution to atherogenesis have not yet been elucidated.To determine whether anabolism is hepatic or intestinal, subfrac- tions of CER-VLDL were characterized at selected intervals from day 0 to 60 of cholesterol feeding.Rate zonal ultracentrifugation of CER-VLDL from rabbits fed cholesterol for 4 and 60 d demonstrated an early increase of the proportion of cho- lesterol carried in the intestinally-derived fraction (designated as Fx-I) of VLDL compared with that in hepatically-derived particles (Fx-H).Quantification by size exclusion HPLC also demonstrated that Fx-I was a prominent CER-VLDL compo- nent at day 4, while Fx-H particles became increasingly promi- nent with further cholesterol feeding.At both 4 and 60 d Fx-I stimulated cholesterol esterification and intracellular choles- terol content in macrophages more than the corresponding Fx-H did.In fact, Fx-H harvested at 4 d produced no choles- terol ester deposition.In contrast, Fx-H harvested at 60 d markedly stimulated cholesterol esterification and intracellular cholesterol content.Thus, both compositional and meta- bolic characteristics of CER-VLDL changed as a function of the duration cholesterol feeding. Methods AnimalsNew Zealand rabbits (2-3 kg) were obtained from an inbred colony maintained at Children's Hospital of St. Louis in the Washington University Medical Center.Animals were fed an ad lib.laboratory diet 1. Abbreviations used in this paper: CER, cholesterol ester-rich.