Abstract 236: Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia
Familial hypobetalipoproteinemia (FHBL) is a codominant disorder of lipoprotein metabolism characterized by decreased plasma concentrations of LDL-cholesterol and apolipoprotein (apo) B. We examined the effect of heterozygous APOB L343V FHBL on fasting and postprandial lipoprotein metabolism. VLDL, IDL-, and LDL-apoB kinetics were determined in the fasting state using stable isotope methods and compartmental modeling. VLDL-apoB concentrations in FHBL subjects (n=2) were reduced by more than 75% compared to healthy, normolipidemic control subjects (P<0.01). VLDL-apoB fractional catabolic rate (FCR) was more than 5-fold higher in the FHBL subjects (P=0.07). ApoB production rates and IDL- and LDL-apoB FCRs were not different between FHBL subjects and controls. To assess postprandial lipoprotein metabolism, a standardized oral fat load was given after a 12 h fast to heterozygous APOB L343V FHBL subjects (n=3) and normolipidemic controls. The postprandial incremental area under the curve (0-10 h) in FHBL subjects was decreased for large TRL-triglyceride (-77%; P<0.0001), small TRL-cholesterol (-83%; P<0.001), small TRL-triglyceride (-88%; P<0.0.001) and plasma apoB (-63%; P<0.0001) compared with controls. Compartmental modeling analysis showed that apoB-48 production was decreased (-91%; P<0.05) compared with controls. We conclude that when compared to controls, APOB L343V FHBL heterozygotes show decreased TRL production with normal postprandial TRL particle clearance. In contrast, VLDL-apoB production was normal, while the FCR was higher in heterozygotes compared with lean control subjects. These mechanisms account for the marked hypolipidemic state observed in these FHBL subjects.
Author Disclosures: A.J. Hooper: None. K. Robertson: None. L.V. Heeks: None. D. Champain: None. P.R. Barrett: None. K.G. Parhofer: None. F.M. van Bockxmeer: None. J.R. Burnett: None.
- © 2014 by American Heart Association, Inc.