In subjects with
hypertriglyceridemia, plasma concentrations of
low density lipoprotein (
LDL) cholesterol are often normal or reduced. Perturbations that alter plasma
very low density lipoprotein (VLDL) concentrations are associated with opposite changes in plasma
LDL levels. To determine the mechanisms regulating plasma
LDL levels, we used 131I-VLDL and 125I-LDL to measure the fractional catabolic rates (FCR), production rates (PR), and rates of interconversion of
apoprotein B (
apo B) in VLDL,
intermediate density lipoprotein, and
LDL in six hypertriglyceridemic subjects pre- and post-
weight reduction. [2-3H]
glycerol was used to quantitate
VLDL triglyceride PR. All data are presented as mean +/- SD. Percent ideal body weight fell from 132 +/- 17.9 to 119 +/- 15.9% in the group, P less than 0.05. After
weight loss, plasma
VLDL triglyceride (486.0 +/- 364.1 vs. 191.3 +/- 65.4 mg/dl, P less than 0.05) and VLDL
apo B (32.2 +/- 12.0 vs. 14.8 +/- 6.8 mg/dl, P less than 0.05) concentrations were reduced.
VLDL triglyceride PR also fell after
weight reduction (56.6 +/- 39.0 vs. 28.6 +/- 23.1 mg/kg per h, P less than 0.05), as did VLDL
apo B PR (47.9 +/- 41.4 vs. 19.0 +/- 14.1 mg/kg per d, P less than 0.05). Pre-
weight loss, plasma
LDL cholesterol and
apo B levels were low-normal or reduced (64.0 +/- 12.6 and 58.4 +/- 11.9 mg/dl, respectively) despite normal or elevated
LDL apo B PR (17.4 +/- 7.2 mg/kg per d). The reduced
cholesterol and
apo B levels were associated with increased FCRs (0.68 +/- 0.29 d-1) and reduced
cholesterol/
protein ratios (1.01 +/- 0.18) in
LDL. The plasma levels of
LDL cholesterol and
apo B rose after
weight reduction (84.8 +/- 24.9, P less than 0.05; and 69.5 +/- 14.3 mg/dl, P less than 0.05, respectively, vs. base line). These increased concentrations resulted from a combination of events. First, the FCR for
LDL apo B fell in five of six subjects with a significant reduction for the group as a whole (0.48 +/- 0.11 d-1, P less than 0.05 vs. base line). Second, the
cholesterol/
protein ratio increased in all six subjects with a significantly greater mean after
weight loss (1.25 +/- 0.27, P less than 0.05 vs. base line). In contrast, the
LDL apo B PR fell or was essentially unchanged in the six subjects after
weight loss (mean, 14.4 +/- 2.8 mg/kg per d; NS vs. pre-
weight loss). The changes in
LDL catabolism and composition were associated with changes in the source of
LDL apo B. Pre-
weight loss, 73.3% of
LDL was derived from VLDL, while 26.7% was directly secreted into plasma. Post-
weight reduction, VLDL-derived
LDL fell to 46.8% of total, while direct secretion accounted for 53.2% of
LDL production. These changes were significant; P < 0.95. Thus, all subjects had direct secretion of
LDL apo B and the magnitude of this source of
VLDL triglyceride secretion. These results indicate that the regulation of plasma
LDL levels in hypertriglyceridemic subjects is quite complex and that the rise in
LDL levels after
weight loss results from reduction in the fractional catabolism of this
lipoprotein. The fall in the FCR is associated with changes in the source of
LDL and in its composition.