Compensatory mechanisms governing the concentration of plasma low density lipoprotein

To evaluate factors regulating the concentrations of plasma low density lipoproteins (LDL), apolipoprotein B metabolism was studied in nine Pima Indians (25 ± 2 yr, 191 ± 20% ideal wt) with low LDL cholesterol (77 ± 7 mg/dl) and apoB (60 ± 4 mg/dl) and in eight age- and weight-matched Caucasians with similar very low density lipoprotein (VLDL) concentrations, but higher LDL (cholesterol = 104 ± 18; apoB = 82 ± 10; P<0.05). Subjects received autologous ¹³¹I-labeled VLDL and ¹²⁵I-labeled LDL, and specific activities of VLDL-apoB, intermediate density lipoprotein (IDL)-apoB, and LDL-apoB were analyzed using a multicompartmental model. Synthesis of LDL-apoB was similar (1224 ± 87 mg/dl in Pimas vs 1218 ± 118 mg/dl in Caucasians) but in Pimas the fractional catabolic rate (FCR) for LDL-apoB was higher (0.48 ± 0.02 vs 0.39 ± 0.04 d^-1, P <0.05). In the Pimas, a much higher proportion of VLDL-apoB was catabolized without conversion to LDL (47 ± 3 vs 30 ± 5%, P < 0.01). When all subjects were considered together, LDL-apoB concentrations were negatively correlated with both FCR for LDL-apoB (r = -0.79, P < 0.0001) and the non-LDL pathway (r = -0.43, P < 0.05). Also, the direct removal (non-LDL) path was correlated with VLDL-apoB production (r = 0.49, P = 0.03), and the direct removal pathway and FCR for LDL-apoB were correlated (r = 0.49, P = 0.03). In conclusion, plasma LDL appear to be regulated by both the catabolism of LDL and the extent of metabolism of VLDL without conversion to LDL; both of these processes may be mediated by the apoB/E receptor, and appear to increase in response to increasing VLDL production.