Lipoprotein metabolism in APOB L343V familial hypobetalipoproteinemia

<p><b>Context:</b>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).</p> <p><b>Objective:</b>The objective was to examine the effect of heterozygous <i>APOB</i> L343V FHBL on postprandial triglyceride-rich lipoprotein (TRL) and fasting lipoprotein metabolism.</p> <p><b>Methods:</b>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.</p> <p><b>Results:</b>The postprandial incremental area under the curve (0-10 h) in FHBL subjects (n = 3) was lower for large TRL-triglyceride (-77%; <i>P</i> < .0001), small TRL-cholesterol (-83%; <i>P</i> < .001), small TRL-triglyceride (-88%; <i>P</i> < .001), and for plasma triglyceride (-70%; <i>P</i> < .01) and apoB (-63%; <i>P</i> < .0001) compared with controls. Compartmental analysis showed that apoB-48 production was lower (-91%; <i>P</i> < .05) compared with controls. VLDL-apoB concentrations in FHBL subjects (n = 2) were lower by more than 75% compared with healthy, normolipidemic control subjects (<i>P</i> < .01). The VLDL-apoB fractional catabolic rate (FCR) was more than 5-fold higher in the FHBL subjects (<i>P</i> = .07). ApoB production rates and IDL- and LDL-apoB FCRs were not different between FHBL subjects and controls.</p> <p><b>Conclusions:</b> 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.</p>