title: Postprandial lipoprotein metabolism in familial hypobetalipoproteinemia.
abstract: OBJECTIVE
  Familial hypobetalipoproteinemia (FHBL) is an autosomal codominantly inherited disorder of lipoprotein metabolism characterized by decreased plasma concentrations of low-density lipoprotein-cholesterol and apolipoprotein (apo) B. We examined the effect of truncated apoB variants (<apoB-48) causing FHBL on postprandial triglyceride-rich lipoprotein (TRL) metabolism.
  
  
  RESULTS
  A standardized oral fat load was given after a 12-h fast to six heterozygous [apoB-6.9 (n=3), apoB-25.8 (n=1), apoB-40.3 (n=2)] FHBL subjects and 10 normolipidemic controls. Plasma was obtained every 2 h for 10 h. Large TRLs [containing chylomicrons (CM)] and small TRLs (containing CM remnants) were isolated by ultracentrifugation. Compared with controls, FHBL subjects had significantly decreased fasting plasma cholesterol (2.3+/-0.5 vs. 4.8+/-0.5 mmol/liter), triglyceride (0.4+/-0.3 vs. 1.5+/-0.5 mmol/liter), low-density lipoprotein-cholesterol (0.6+/-0.4 vs. 3.0+/-0.5 mmol/liter), and apoB (0.22+/-0.05 vs. 0.95+/-0.14 g/liter) concentrations (all P<0.001). The postprandial incremental area under the curve in FHBL subjects was decreased for large TRL-triglyceride (-61%; P<0.005), small TRL-cholesterol (-86%; P<0.001), and small TRL-triglyceride (-86%; P<0.001) relative to controls. Multicompartmental modeling analysis showed that the delay time of apoB-48 was shorter and that apoB-48 production was decreased in FHBL subjects compared with controls.
  
  
  CONCLUSIONS
  We have demonstrated that heterozygous FHBL subjects with apoB truncations shorter than apoB-48, and therefore only a single fully-functional apoB-48 allele, have decreased TRL production but normal postprandial TRL particle clearance.
authors.affiliation: Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Wellington Street, GPO Box X2213, Perth, and School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hooper
authors.forename: Ken
authors.initials: K
authors.lastname: Robertson
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Parhofer
authors.forename: Frank M
authors.initials: FM
authors.lastname: van Bockxmeer
authors.forename: John R
authors.initials: JR
authors.lastname: Burnett
mesh_terms: D000328:Adult; D053283:Apolipoprotein B-48 / Q000097:blood* / Q000235:genetics; D001774:Blood Chemical Analysis; D015992:Body Mass Index; D004041:Dietary Fats; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood*; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008954:Models, Biological; D019518:Postprandial Period
chemical_list: D053283:Apolipoprotein B-48; D004041:Dietary Fats; D008055:Lipids; D008074:Lipoproteins