Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia.

Amanda Hooper, L. Heeks, Kenneth Robertson, Danie Champain, J. Hua, S. Song, P. Parhofer, Hugh Barrett, Frank Van Bockxmeer, John Burnett

    Research output: Contribution to journalArticle

    4 Citations (Scopus)
    87 Downloads (Pure)

    Abstract

    Context: 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. - See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2015-2731#sthash.roa6afj8.dpuf
    Original languageEnglish
    Pages (from-to)E1484-E1490
    Number of pages7
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume100
    Issue number11
    Early online date31 Aug 2015
    DOIs
    Publication statusPublished - Nov 2015

    Fingerprint

    Hypobetalipoproteinemias
    Apolipoproteins B
    Metabolism
    Lipoproteins
    Triglycerides
    VLDL Lipoproteins
    Apolipoprotein B-48
    IDL Lipoproteins
    Heterozygote
    Plasmas
    LDL Lipoproteins
    Area Under Curve
    Fasting
    Kinetics
    Familial Hypobetalipoproteinemia
    Isotopes
    LDL Cholesterol
    Eating
    Fats

    Cite this

    Hooper, Amanda ; Heeks, L. ; Robertson, Kenneth ; Champain, Danie ; Hua, J. ; Song, S. ; Parhofer, P. ; Barrett, Hugh ; Van Bockxmeer, Frank ; Burnett, John. / Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 11. pp. E1484-E1490.
    @article{d454844d18ba40c38a1c595e99dd2750,
    title = "Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia.",
    abstract = "Context: 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. - See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2015-2731#sthash.roa6afj8.dpuf",
    author = "Amanda Hooper and L. Heeks and Kenneth Robertson and Danie Champain and J. Hua and S. Song and P. Parhofer and Hugh Barrett and {Van Bockxmeer}, Frank and John Burnett",
    year = "2015",
    month = "11",
    doi = "10.1210/jc.2015-2731",
    language = "English",
    volume = "100",
    pages = "E1484--E1490",
    journal = "Journal of Endocrinology & Metabolism",
    issn = "0021-972X",
    publisher = "ENDOCRINE SOC",
    number = "11",

    }

    Hooper, A, Heeks, L, Robertson, K, Champain, D, Hua, J, Song, S, Parhofer, P, Barrett, H, Van Bockxmeer, F & Burnett, J 2015, 'Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia.' Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 11, pp. E1484-E1490. https://doi.org/10.1210/jc.2015-2731

    Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia. / Hooper, Amanda; Heeks, L.; Robertson, Kenneth; Champain, Danie; Hua, J.; Song, S.; Parhofer, P.; Barrett, Hugh; Van Bockxmeer, Frank; Burnett, John.

    In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 11, 11.2015, p. E1484-E1490.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia.

    AU - Hooper, Amanda

    AU - Heeks, L.

    AU - Robertson, Kenneth

    AU - Champain, Danie

    AU - Hua, J.

    AU - Song, S.

    AU - Parhofer, P.

    AU - Barrett, Hugh

    AU - Van Bockxmeer, Frank

    AU - Burnett, John

    PY - 2015/11

    Y1 - 2015/11

    N2 - Context: 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. - See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2015-2731#sthash.roa6afj8.dpuf

    AB - Context: 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. - See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2015-2731#sthash.roa6afj8.dpuf

    U2 - 10.1210/jc.2015-2731

    DO - 10.1210/jc.2015-2731

    M3 - Article

    VL - 100

    SP - E1484-E1490

    JO - Journal of Endocrinology & Metabolism

    JF - Journal of Endocrinology & Metabolism

    SN - 0021-972X

    IS - 11

    ER -