© 1997 American Heart Association, Inc.
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Decreased Production and Increased Catabolism of Apolipoprotein B-100 in Apolipoprotein B-67/B-100 Heterozygotes
From the Lipid Metabolism Laboratory, Jean Meyer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (F.K.W., A.H.L., G.G.D., J.M.O., E.J.S.); and the Resource Facility for Kinetic Analysis, Center for Bioengineering, University of Washington, Seattle (P.H.R.B.).
Correspondence to Francine K. Welty, Lipid Metabolism Lab, HNRC at Tufts University, 711 Washington St, Boston, MA 02111. E-mail fwelty{at}nedhmail.nedh.harvard.edu
Abstract Apolipoprotein (apo) B-67 is a truncated form of apoB-100 due to deletion of an adenine at cDNA 9327. Heterozygotes have one allele making apoB-100; therefore, plasma apoB levels would be predicted to be at least 50% of normal. However, apoB-67 heterozygotes have total plasma apoB levels that are 24% of normal. To determine the mechanisms responsible for the lower-than-expected levels of apoB, in vivo kinetics of apoB-100 were performed in three apoB-67/apoB-100 heterozygotes and compared with those of six control subjects by using a primed-constant infusion of [5,5,5-2H3]leucine in the fed state. Kinetic parameters were calculated by multicompartmental modeling of the data. The mean total apoB plasma concentration of the apoB-67 subjects was 21.8±6.1 mg/dL, or 24% of that of control subjects (89.6±24.1 mg/dL, P=.002). ApoB-67 subjects had lower mean VLDL apoB-100 production rates (3.6±1.2 versus 13.9±3.5 mg·kg-1·d-1, P=.002) and lower mean transport rates of apoB-100 into LDL (3.5±1.4 versus 12.6±4.1 mg·kg-1·d-1, P=.008) compared with control subjects. The transport rate into IDL was not significantly different (1.2±0.5 versus 6.2±4.0 mg·kg-1·d-1, P=.07). The fractional catabolic rate of VLDL apoB-100 was significantly higher in apoB-67 subjects than in control subjects (18.1±8.6 versus 7.6±1.6 mg·kg-1·d-1, P=.017). ApoB-100 IDL and LDL fractional catabolic rates were not significantly different. VLDL apoB-100 pool size in apoB-67 subjects was 11% of that of control subjects (15.8±7.7 versus 141.6±33.7 mg, P=.0004) due to a 74% lower production rate (26% of control values) and a 2.4-fold higher fractional catabolic rate. LDL apoB-100 pool size in apoB-67 subjects was 22% of that of control subjects (665.3±192.4 versus 2968.3±765.2 mg, P=.002) due primarily to a lower production rate (27% of control values). Thus, both decreased production of VLDL and LDL apoB-100 and increased catabolism of VLDL apoB-100 are responsible for the low levels of apoB-100 in apoB-67 subjects.
Key Words: hypobetalipoproteinemia • apolipoprotein B • kinetics • metabolism • deuterium
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