INCREASED CATABOLIC RATE OF LOW-DENSITY LIPOPROTEINS IN HUMANS WITH CHOLESTERYL ESTER TRANSFER PROTEIN-DEFICIENCY

The cholesteryl ester transfer protein (CETP) transfers lipids among l ipoprotein particles and plays a central role in lipoprotein metabolis m, Humans with genetic deficiency of CETP have both elevated HDL chole sterol and apolipoprotein A-I concentrations as well as decreased LDL cholesterol and apolipoprotein B levels, The present study was underta ken to elucidate the metabolic basis for the decreased LDL cholesterol and apo B levels in CETP deficiency, We conducted a series of in vivo apo B kinetic studies in two unrelated homozygotes with CETP deficien cy and in control subjects. A primed constant infusion of stable isoto pically labeled phenylalanine was administered to the two CETP deficie nt subjects and control subjects and apo B kinetic parameters in VLDL, intermediate density lipoproteins, and LDL were obtained by using a m ulticompartmental model, The fractional catabolic rates (FCR) of LDL a po B were significantly increased in the CETP-deficient subjects (0.56 and 0.75/d) compared with the controls (mean FCR of 0.39/d), Furtherm ore, the production rates of apo B in VLDL and intermediate density li poprotein were decreased by 55% and 81%, respectively, in CETP deficie ncy compared with the controls, In conclusion, CETP-deficient subjects were demonstrated to have substantially increased catabolic rates of LDL apo B as the primary metabolic basis for the low plasma levels of LDL apo B, This result indicates that the LDL receptor pathway may be up-regulated in CETP deficiency.