Decreased production rates of VLDL triglycerides and ApoB-100 in subjects heterozygous for familial hypobetalipoproteinemia

Familial hypobetalipoproteinemia: (FHBL) is an autosomal codominant disorde r characterized by low levels of apolipoprotein (apo) B and low-density lip oprotein (LDL) cholesterol. Decreased production rates of apoB have been de monstrated in vivo in FHBL heterozygotes. In the present study, we wished t o investigate whether the transport of triglycerides was similarly affected in these subjects. Therefore, we studied the in vivo kinetics of very-low- density lipoprotein (VLDL) triglycerides and VLDL apoB-100 simultaneously i n 7 FHBL heterozygotes from 2 well-characterized kindreds and 7 healthy nor molipidemic subjects. In both kindreds, hypobetalipoproteinemia is caused b y mutations in the 5' portion of the apoB gene specifying short truncations of apoB undetectable in plasma. A bolus injection of deuterated palmitate and a primed constant infusion of deuterated leucine were given simultaneou sly, and their incorporation into VLDL triglycerides and VLDL apoB, respect ively, were determined by gas chromatography-mass spectrometry. Kinetic par ameters were calculated by using compartmental modeling. VLDL apoB fraction al catabolic rates (FCRs) in FHBL heterozygotes and controls were similar ( 11.6 +/- 3.9 and 10.9 +/- 2.4 pools per day, respectively, P = 0.72). On th e other hand, FHBL heterozygotes had a 75% decrease in VLDL apoB production rates compared with normal subjects (5.8 +/- 1.8 versus 23.4 +/- 7.1 mg/kg per day, P < 0.001). The decreased production rates of VLDL apoB accounts for the very low concentrations of plasma apoB found in heterozygotes from these kindreds (24% of normal). Mean VLDL triglyceride FCRs in FHBL subject s and controls were not significantly different (1.06 +/- 0.74 versus 0.89 +/- 0.50 pools per hour, respectively, P = 0.61). There was a good correlat ion between VLDL apoB FCR and VLDL triglyceride FCR in the 2 groups (r = 0. 84, P < 0.001). VLDL triglyceride production rates were decreased by 60% in FHBL heterozygotes compared with controls (9.3 +/- 6.0 versus 23.0 +/- 9.6 mu mol/kg per hour, P = 0.008). Thus, the hepatic secretion of VLDL trigly cerides is reduced in FHBL heterozygotes but to a lesser extent than the de crease in apoB-100 secretion. This is probably achieved by the secretion of VLDL particles enriched with triglycerides.