LDL and apoB
Bile acid sequestrant cholebine shrinks large light LDL without touching CETP or LCAT activity (Atherosclerosis 1997)
Original title: Specific reduction of plasma large, light low-density lipoprotein by a bile acid sequestering resin, cholebine (MCI-196) in type II hyperlipoproteinemia
In 16 patients with type II hyperlipoproteinemia, twelve weeks of the bile acid sequestrant cholebine (3 g/day) reduced total cholesterol by 8.3 plus or minus 8.1% and LDL cholesterol by 14.4 plus or minus 11.9% (P less than 0.001) without affecting HDL cholesterol. Gradient polyacrylamide gel electrophoresis showed cholebine specifically reduced large, light LDL1 cholesterol by 22.9 plus or minus 18.9% (P less than 0.001) while sparing VLDL, IDL, small LDL2, and HDL subfractions. To probe the mechanism, LCAT and CETP activities were assayed and neither was altered by cholebine, while LDL-receptor activity in cultured lymphocytes correlated negatively with the reductions in LDL-C, IDL-C, and LDL1-C, indicating cholebine acts through stimulated hepatic LDL-receptor activity rather than through CETP or LCAT.
Original abstract
The effect of a bile acid sequestrant, cholebine (3 g/day), on plasma lipoprotein subfractions was investigated in 16 patients with type II hyperlipoproteinemia. Activities of low density lipoprotein (LDL)-receptor and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) were assayed to address the mechanism of cholebine-induced changes in plasma lipoprotein subfractions. Twelve weeks of treatment with cholebine reduced plasma levels of total cholesterol (TC) and LDL-cholesterol (C) by 8.3 +/- 8.1% (mean +/- S.D.) and 14.4 +/- 11.9%, respectively (P < 0.001), but did not affect plasma levels of high density lipoprotein (HDL)-C. Cholebine significantly reduced plasma levels of LDL1-C (1.019 < d < 1.045) by 22.9 +/- 18.9% (P < 0.001) but did not affect plasma levels of very low density lipoprotein (VLDL)-C, intermediate density lipoprotein (IDL)-C, LDL2-C (1.045 < d < 1.063), HDL2-C, and HDL3-C (d > 1.125). Gradient polyacrylamide gel electrophoresis (PAGE) revealed that cholebine reduced large LDL in plasma but had almost no effects on small LDL and HDL subfractions. Cholebine did not alter the activities of LCAT and CETP. LDL-receptor activities of cultured lymphocytes negatively correlated with the reduction in plasma levels of LDL-C (r = -0.500, P < 0.05), IDL-C (r = -0.581, P < 0.02), and LDL1-C (r = -0.610, P < 0.01), respectively. Thus, cholebine seems to reduce further the plasma levels of IDL and large, light LDL in patients with lower LDL-receptor activities. We conclude that cholebine only reduces plasma levels of large, light LDL. This may be due to the stimulation of hepatic LDL-receptor activity.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.