Familial hypobetalipoproteinemia (FHBL) is an autosomal codominant disorder characterized by low levels of
apolipoprotein (
apo) B and
low-density lipoprotein (
LDL) cholesterol. Decreased production rates of
apoB have been demonstrated in vivo in FHBL heterozygotes. In the present study, we wished to 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 in 7 FHBL heterozygotes from 2 well-characterized kindreds and 7 healthy normolipidemic subjects. In both kindreds,
hypobetalipoproteinemia is caused by 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 simultaneously, and their incorporation into VLDL
triglycerides and VLDL
apoB, respectively, were determined by gas chromatography-mass spectrometry. Kinetic parameters were calculated by using compartmental modeling. VLDL
apoB fractional 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 the 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 subjects 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 correlation 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 micromol/kg per hour, P=0.008). Thus, the hepatic secretion of VLDL
triglycerides is reduced in FHBL heterozygotes but to a lesser extent than the decrease in
apoB-100 secretion. This is probably achieved by the secretion of VLDL particles enriched with
triglycerides.