title: Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia.
abstract: BACKGROUND
  Familial hypobetalipoproteinemia (FHBL) is a codominant disorder of lipoprotein metabolism characterized by decreased plasma concentrations of low-density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB).
  
  
  OBJECTIVE
  The objective was to examine the effect of heterozygous APOB L343V FHBL on postprandial triglyceride-rich lipoprotein (TRL) and fasting lipoprotein metabolism.
  
  
  METHODS
  Plasma incremental area under the curve apoB-48 and apoB-48 kinetics were determined after ingestion of a standardized oral fat load using compartmental modeling. Very low-density lipoprotein (VLDL)-, intermediate-density lipoprotein (IDL)-, and LDL-apoB kinetics were determined in the fasting state using stable isotope methods and compartmental modeling.
  
  
  RESULTS
  The postprandial incremental area under the curve (0-10 h) in FHBL subjects (n = 3) was lower for large TRL-triglyceride (-77%; P < .0001), small TRL-cholesterol (-83%; P < .001), small TRL-triglyceride (-88%; P < .001), and for plasma triglyceride (-70%; P < .01) and apoB (-63%; P < .0001) compared with controls. Compartmental analysis showed that apoB-48 production was lower (-91%; P < .05) compared with controls. VLDL-apoB concentrations in FHBL subjects (n = 2) were lower by more than 75% compared with healthy, normolipidemic control subjects (P < .01). The VLDL-apoB fractional catabolic rate (FCR) was more than 5-fold higher in the FHBL subjects (P = .07). ApoB production rates and IDL- and LDL-apoB FCRs were not different between FHBL subjects and controls.
  
  
  CONCLUSIONS
  We conclude that when compared to controls, APOB L343V FHBL heterozygotes show lower TRL production with normal postprandial TRL particle clearance. In contrast, VLDL-apoB production was normal, whereas the FCR was higher in heterozygotes compared with lean control subjects. These mechanisms account for the marked hypolipidemic state observed in these FHBL subjects.
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: Amanda J
authors: AJ
authors: Hooper
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: Liesl
authors: L
authors: Heeks
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: Ken
authors: K
authors: Robertson
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: Danie
authors: D
authors: Champain
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: Jianmin
authors: J
authors: Hua
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: Swithin
authors: S
authors: Song
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: Klaus G
authors: KG
authors: Parhofer
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: P Hugh R
authors: PH
authors: Barrett
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: Frank M
authors: FM
authors: van Bockxmeer
authors: Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.
authors: John R
authors: JR
authors: Burnett
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D053283:Apolipoprotein B-48 / Q000097:blood / Q000378:metabolism; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D015536:Down-Regulation; D005260:Female; D006579:Heterozygote; D006801:Humans; D052476:Hypobetalipoproteinemia, Familial, Apolipoprotein B / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D053419:Lipoproteins, IDL / Q000097:blood / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D008297:Male; D062407:Meals; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism
chemical_list: D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides