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
C2 - 26323024
SN - 0021-972X
VL - 100
SP - E1484-E1490
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -